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    Celia A Schiffer PhD

    TitleProfessor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentBiochemistry and Molecular Pharmacology
    AddressUniversity of Massachusetts Medical School
    364 Plantation Street, LRB
    Worcester MA 01605
    Phone508-856-8008
      Other Positions
      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentBiochemistry and Molecular Pharmacology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentBioinformatics and Computational Biology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentInterdisciplinary Graduate Program

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentMD/PhD Program

      InstitutionUMMS - Programs, Centers and Institutes
      DepartmentBioinformatics and Integrative Biology

      InstitutionUMMS - Programs, Centers and Institutes
      DepartmentCenter for AIDS Research

      InstitutionUMMS - Programs, Centers and Institutes
      DepartmentChemical Biology

        Overview 
        Narrative

        Academic Background

        B.A., University of Chicago, 1986
        Ph.D., University of California, San Francisco, 1992


        Postdoctoral Fellow, ETH-Zurich, 1992-94
        Postdoctoral Fellow, Genentech, 1994-97

        Director of the Center for AIDS Research (CFAR)

        Structural basis for molecular recognition in HIV Protease

        Photo: Celia A. SchifferMany biological processes involve complex interdependent molecular recognition events, in which molecules recognize each other with high specificity. Such events include an enzyme acting on its substrate in catalysis, a ligand activating a receptor in regulation and a two dimensional peptide chain assembling into a specific three dimensional fold. The specificity of such molecular recognition events can only be thoroughly understood by detailed analyses of the structures, functions and flexibilities of the molecules.

        Investigating molecular recognition of biological macromolecules at the atomic level has been the central objective of my research. In my group we address these questions by using detailed structural and dynamic analyses (both experimental and computational) combined with functional and biophysical assays. This comprehensive approach is essential as molecular recognition is a dynamic event; usually, at least one of the molecular surfaces needs to undergo a conformational change to recognize the other.

        Disruption of the life cycle of HIV, the virus that causes AIDS, is the goal of the drugs used to treat infected pediatric patients. The most successful drugs are the protease inhibitors. As the individual virus particles assemble, a series of their necessary components are attached together. For the virus particles to mature and become infectious these necessary components must be cut apart. The protease is the "scissors" molecule which "knows" where to sever these components. Protease inhibitors block these scissors and prevent the virus from maturing. Unfortunately, the virus changes (mutates) and alters the protease so that the inhibitors no longer block the "scissors" action, and the virus is once again infectious (drug resistant). Our strategy is to examine how the protease "knows" where to cut and how this "knowledge" is changed when the protease becomes drug resistant. By understanding how the protease changes, our data will be complementary to the existing efforts of the pharmaceutical industry.

        Figure

        complex with the peptide that releases the capsid protein

        In the maturation of the human immunodeficiency virus, HIV proteasespecifically recognizes and cleaves nine non-homologous sites in the gag-polpolyproteins. How this symmetric homodimeric protein is able to specificallyrecognize not only a single substrate, but a variety of substrate sequencesposes fascinating questions of molecular recognition. What allowsone molecule to recognize, bind, cleave and release others? To elucidatethis specificity, our laboratory has solved for the first time structuresof substrate complexes of HIV protease with an inactive variant of HIVprotease. The complex with the peptide that releases the capsidprotein is shown above. These structures are then starting pointsfor molecular dynamics simulations to probe the conformational adaptabilityof this protease, its substrates and the solvent environment. Inaddition as drug resistant mutations occur the specificity of the proteasechanges, we are elucidating these changes with phage display, enzyme kineticsand crystal structures of drug resistant proteases bound to inhibitors.



        Rotation Projects

        Possible Rotation Projects

        1. Site directed mutagenesis and enzyme kinetics of HIV protease to determine the role of strongly conserved residues.
        2. Refinement of crystal structures of HIV protease in complex with substrates or inhibitors
        3. Analysis of molecular dynamics trajectories of HIV protease. Analysis of the water, peptide and protein structure.


        Bibliographic 
        selected publications
        List All   |   Timeline
        1. Schiffer C. Interview with celia schiffer. Future Med Chem. 2013 Jul; 5(11):1193-7.
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        2. Bohn MF, Shandilya SM, Albin JS, Kouno T, Anderson BD, McDougle RM, Carpenter MA, Rathore A, Evans L, Davis AN, Zhang J, Lu Y, Somasundaran M, Matsuo H, Harris RS, Schiffer CA. Crystal Structure of the DNA Cytosine Deaminase APOBEC3F: The Catalytically Active and HIV-1 Vif-Binding Domain. Structure. 2013 Jun 4; 21(6):1042-50.
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        3. Mittal S, Bandaranayake RM, King NM, Prabu-Jeyabalan M, Nalam MN, Nalivaika EA, Kurt Yilmaz N, Schiffer CA. Structural and Thermodynamic Basis of Amprenavir/Darunavir and Atazanavir Resistance in HIV-1 Protease with Mutations at Residue 50. J Virol. 2013 Apr; 87(8):4176-84.
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        4. Foulkes-Murzycki JE, Rosi C, Kurt Yilmaz N, Shafer RW, Schiffer CA. Cooperative Effects of Drug-Resistance Mutations in the Flap Region of HIV-1 Protease. ACS Chem Biol. 2013 Mar 15; 8(3):513-8.
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        5. Babrzadeh F, Varghese V, Pacold M, Liu TF, Nyrén P, Schiffer C, Fessel WJ, Shafer RW. Collinearity of protease mutations in HIV-1 samples with high-level protease inhibitor class resistance. J Antimicrob Chemother. 2013 Feb; 68(2):414-8.
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        6. Carpenter MA, Li M, Rathore A, Lackey L, Law EK, Land AM, Leonard B, Shandilya SM, Bohn MF, Schiffer CA, Brown WL, Harris RS. Methylcytosine and Normal Cytosine Deamination by the Foreign DNA Restriction Enzyme APOBEC3A. J Biol Chem. 2012 Oct 5; 287(41):34801-8.
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        7. Mruk K, Shandilya SM, Blaustein RO, Schiffer CA, Kobertz WR. Structural insights into neuronal K+ channel-calmodulin complexes. Proc Natl Acad Sci U S A. 2012 Aug 21; 109(34):13579-83.
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        8. Romano KP, Ali A, Aydin C, Soumana D, Ozen A, Deveau LM, Silver C, Cao H, Newton A, Petropoulos CJ, Huang W, Schiffer CA. The Molecular Basis of Drug Resistance against Hepatitis C Virus NS3/4A Protease Inhibitors. PLoS Pathog. 2012 Jul; 8(7):e1002832.
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        9. Parai MK, Huggins DJ, Cao H, Nalam MN, Ali A, Schiffer CA, Tidor B, Rana TM. Design, Synthesis, and Biological and Structural Evaluations of Novel HIV-1 Protease Inhibitors To Combat Drug Resistance. J Med Chem. 2012 Jul 26; 55(14):6328-41.
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        10. King NM, Prabu-Jeyabalan M, Bandaranayake RM, Nalam MN, Nalivaika EA, Ozen A, Haliloglu T, Yilmaz NK, Schiffer CA. Extreme Entropy-Enthalpy Compensation in a Drug-Resistant Variant of HIV-1 Protease. ACS Chem Biol. 2012 Sep 21; 7(9):1536-46.
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        11. Alvizo O, Mittal S, Mayo SL, Schiffer CA. Structural, kinetic, and thermodynamic studies of specificity designed HIV-1 protease. Protein Sci. 2012 Jul; 21(7):1029-41.
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        12. Myint W, Cai Y, Schiffer CA, Ishima R. Quantitative comparison of errors in (15)N transverse relaxation rates measured using various CPMG phasing schemes. J Biomol NMR. 2012 May; 53(1):13-23.
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        13. Mittal S, Cai Y, Nalam MN, Bolon DN, Schiffer CA. Hydrophobic Core Flexibility Modulates Enzyme Activity in HIV-1 Protease. J Am Chem Soc. 2012 Mar 7; 134(9):4163-8.
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        14. Lee SK, Potempa M, Kolli M, Ozen A, Schiffer CA, Swanstrom R. Context Surrounding Processing Sites Is Crucial in Determining Cleavage Rate of a Subset of Processing Sites in HIV-1 Gag and Gag-Pro-Pol Polyprotein Precursors by Viral Protease. J Biol Chem. 2012 Apr 13; 287(16):13279-90.
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        15. Li M, Shandilya SM, Carpenter MA, Rathore A, Brown WL, Perkins AL, Harki DA, Solberg J, Hook DJ, Pandey KK, Parniak MA, Johnson JR, Krogan NJ, Somasundaran M, Ali A, Schiffer CA, Harris RS. First-In-Class Small Molecule Inhibitors of the Single-Strand DNA Cytosine Deaminase APOBEC3G. ACS Chem Biol. 2012 Mar 16; 7(3):506-17.
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        16. Cai Y, Schiffer C. Decomposing the Energetic Impact of Drug-Resistant Mutations: The Example of HIV-1 Protease-DRV Binding. Methods Mol Biol. 2012; 819:551-60.
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        17. Auclair JR, Somasundaran M, Green KM, Evans JE, Schiffer CA, Ringe D, Petsko GA, Agar JN. Mass spectrometry tools for analysis of intermolecular interactions. Methods Mol Biol. 2012; 896:387-98.
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        18. Dierynck I, Van Marck H, Van Ginderen M, Jonckers TH, Nalam MN, Schiffer CA, Raoof A, Kraus G, Picchio G. TMC310911, a Novel Human Immunodeficiency Virus Type 1 Protease Inhibitor, Shows In Vitro an Improved Resistance Profile and Higher Genetic Barrier to Resistance Compared with Current Protease Inhibitors. Antimicrob Agents Chemother. 2011 Dec; 55(12):5723-31.
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        19. Ozen A, Haliloglu T, Schiffer CA. Dynamics of Preferential Substrate Recognition in HIV-1 Protease: Redefining the Substrate Envelope. J Mol Biol. 2011 Jul 22; 410(4):726-44.
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        20. Anderson AC, Pollastri MP, Schiffer CA, Peet NP. The challenge of developing robust drugs to overcome resistance. Drug Discov Today. 2011 Sep; 16(17-18):755-61.
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        21. Romano KP, Laine JM, Deveau LM, Cao H, Massi F, Schiffer CA. Molecular Mechanisms of Viral and Host Cell Substrate Recognition by Hepatitis C Virus NS3/4A Protease. J Virol. 2011 Jul; 85(13):6106-16.
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        22. Parry CM, Kolli M, Myers RE, Cane PA, Schiffer C, Pillay D. Three Residues in HIV-1 Matrix Contribute to Protease Inhibitor Susceptibility and Replication Capacity. Antimicrob Agents Chemother. 2011 Mar; 55(3):1106-13.
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        23. Romano KP, Ali A, Royer WE, Schiffer CA. Drug resistance against HCV NS3/4A inhibitors is defined by the balance of substrate recognition versus inhibitor binding. Proc Natl Acad Sci U S A. 2010 Dec 7; 107(49):20986-91.
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        24. Ali A, Bandaranayake RM, Cai Y, King NM, Kolli M, Mittal S, Murzycki JF, Nalam MN, Nalivaika EA, Ozen A, Prabu-Jeyabalan MM, Thayer K, Schiffer CA. Molecular Basis for Drug Resistance in HIV-1 Protease. Viruses. 2010 Nov; 2(11):2509-35.
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        25. Ali A, Reddy GS, Nalam MN, Anjum SG, Cao H, Schiffer CA, Rana TM. Structure-based design, synthesis, and structure-activity relationship studies of HIV-1 protease inhibitors incorporating phenyloxazolidinones. J Med Chem. 2010 Nov 11; 53(21):7699-708.
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        26. Straza MW, Paliwal S, Kovi RC, Rajeshkumar B, Trenh P, Parker D, Whalen GF, Lyle S, Schiffer CA, Grossman SR. Therapeutic targeting of C-terminal binding protein in human cancer. Cell Cycle. 2010 Sep; 9(18):3740-50.
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        27. Ozer N, Schiffer CA, Haliloglu T. Rationale for more diverse inhibitors in competition with substrates in HIV-1 protease. Biophys J. 2010 Sep 8; 99(5):1650-9.
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        28. Bandaranayake RM, Kolli M, King NM, Nalivaika EA, Heroux A, Kakizawa J, Sugiura W, Schiffer CA. The effect of clade-specific sequence polymorphisms on HIV-1 protease activity and inhibitor resistance pathways. J Virol. 2010 Oct; 84(19):9995-10003.
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        29. Nalam MN, Ali A, Altman MD, Reddy GS, Chellappan S, Kairys V, Ozen A, Cao H, Gilson MK, Tidor B, Rana TM, Schiffer CA. Evaluating the substrate-envelope hypothesis: structural analysis of novel HIV-1 protease inhibitors designed to be robust against drug resistance. J Virol. 2010 May; 84(10):5368-78.
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        30. Shandilya SM, Nalam MN, Nalivaika EA, Gross PJ, Valesano JC, Shindo K, Li M, Munson M, Royer WE, Harjes E, Kono T, Matsuo H, Harris RS, Somasundaran M, Schiffer CA. Crystal structure of the APOBEC3G catalytic domain reveals potential oligomerization interfaces. Structure. 2010 Jan 13; 18(1):28-38.
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        31. Kairys V, Gilson MK, Lather V, Schiffer CA, Fernandes MX. Toward the design of mutation-resistant enzyme inhibitors: further evaluation of the substrate envelope hypothesis. Chem Biol Drug Des. 2009 Sep; 74(3):234-45.
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        32. Kolli M, Stawiski E, Chappey C, Schiffer CA. Human immunodeficiency virus type 1 protease-correlated cleavage site mutations enhance inhibitor resistance. J Virol. 2009 Nov; 83(21):11027-42.
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        33. Jorissen RN, Reddy GS, Ali A, Altman MD, Chellappan S, Anjum SG, Tidor B, Schiffer CA, Rana TM, Gilson MK. Additivity in the analysis and design of HIV protease inhibitors. J Med Chem. 2009 Feb 12; 52(3):737-54.
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        34. Anderson J, Schiffer C, Lee SK, Swanstrom R. Viral protease inhibitors. Handb Exp Pharmacol. 2009; (189):85-110.
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        35. Nalam MN, Schiffer CA. New approaches to HIV protease inhibitor drug design II: testing the substrate envelope hypothesis to avoid drug resistance and discover robust inhibitors. Curr Opin HIV AIDS. 2008 Nov; 3(6):642-6.
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        36. Chen W, Lam SS, Srinath H, Jiang Z, Correia JJ, Schiffer CA, Fitzgerald KA, Lin K, Royer WE. Insights into interferon regulatory factor activation from the crystal structure of dimeric IRF5. Nat Struct Mol Biol. 2008 Nov; 15(11):1213-20.
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        37. Lefebvre E, Schiffer CA. Resilience to resistance of HIV-1 protease inhibitors: profile of darunavir. AIDS Rev. 2008 Jul-Sep; 10(3):131-42.
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        38. Bandaranayake RM, Prabu-Jeyabalan M, Kakizawa J, Sugiura W, Schiffer CA. Structural analysis of human immunodeficiency virus type 1 CRF01_AE protease in complex with the substrate p1-p6. J Virol. 2008 Jul; 82(13):6762-6.
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        39. Altman MD, Ali A, Reddy GS, Nalam MN, Anjum SG, Cao H, Chellappan S, Kairys V, Fernandes MX, Gilson MK, Schiffer CA, Rana TM, Tidor B. HIV-1 protease inhibitors from inverse design in the substrate envelope exhibit subnanomolar binding to drug-resistant variants. J Am Chem Soc. 2008 May 14; 130(19):6099-113.
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        40. Chen W, Srinath H, Lam SS, Schiffer CA, Royer WE, Lin K. Contribution of Ser386 and Ser396 to activation of interferon regulatory factor 3. J Mol Biol. 2008 May 30; 379(2):251-60.
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        41. Altman MD, Nalivaika EA, Prabu-Jeyabalan M, Schiffer CA, Tidor B. Computational design and experimental study of tighter binding peptides to an inactivated mutant of HIV-1 protease. Proteins. 2008 Feb 15; 70(3):678-94.
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        42. Auclair JR, Green KM, Shandilya S, Evans JE, Somasundaran M, Schiffer CA. Mass spectrometry analysis of HIV-1 Vif reveals an increase in ordered structure upon oligomerization in regions necessary for viral infectivity. Proteins. 2007 Nov 1; 69(2):270-84.
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        43. Reddy GS, Ali A, Nalam MN, Anjum SG, Cao H, Nathans RS, Schiffer CA, Rana TM. Design and synthesis of HIV-1 protease inhibitors incorporating oxazolidinones as P2/P2' ligands in pseudosymmetric dipeptide isosteres. J Med Chem. 2007 Sep 6; 50(18):4316-28.
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        44. Chellappan S, Kairys V, Fernandes MX, Schiffer C, Gilson MK. Evaluation of the substrate envelope hypothesis for inhibitors of HIV-1 protease. Proteins. 2007 Aug 1; 68(2):561-7.
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        45. Nalam MN, Peeters A, Jonckers TH, Dierynck I, Schiffer CA. Crystal structure of lysine sulfonamide inhibitor reveals the displacement of the conserved flap water molecule in human immunodeficiency virus type 1 protease. J Virol. 2007 Sep; 81(17):9512-8.
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        46. Chellappan S, Kiran Kumar Reddy GS, Ali A, Nalam MN, Anjum SG, Cao H, Kairys V, Fernandes MX, Altman MD, Tidor B, Rana TM, Schiffer CA, Gilson MK. Design of mutation-resistant HIV protease inhibitors with the substrate envelope hypothesis. Chem Biol Drug Des. 2007 May; 69(5):298-313.
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        47. Chen W, Lam SS, Srinath H, Schiffer CA, Royer WE, Lin K. Competition between Ski and CREB-binding protein for binding to Smad proteins in transforming growth factor-beta signaling. J Biol Chem. 2007 Apr 13; 282(15):11365-76.
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        48. Foulkes-Murzycki JE, Scott WR, Schiffer CA. Hydrophobic sliding: a possible mechanism for drug resistance in human immunodeficiency virus type 1 protease. Structure. 2007 Feb; 15(2):225-33.
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        49. Ali A, Reddy GS, Cao H, Anjum SG, Nalam MN, Schiffer CA, Rana TM. Discovery of HIV-1 protease inhibitors with picomolar affinities incorporating N-aryl-oxazolidinone-5-carboxamides as novel P2 ligands. J Med Chem. 2006 Dec 14; 49(25):7342-56.
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        50. Mitsuya Y, Winters MA, Fessel WJ, Rhee SY, Hurley L, Horberg M, Schiffer CA, Zolopa AR, Shafer RW. N88D facilitates the co-occurrence of D30N and L90M and the development of multidrug resistance in HIV type 1 protease following nelfinavir treatment failure. AIDS Res Hum Retroviruses. 2006 Dec; 22(12):1300-5.
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        51. Forget AL, Kudron MM, McGrew DA, Calmann MA, Schiffer CA, Knight KL. RecA dimers serve as a functional unit for assembly of active nucleoprotein filaments. Biochemistry. 2006 Nov 14; 45(45):13537-42.
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        52. Ozer N, Haliloglu T, Schiffer CA. Substrate specificity in HIV-1 protease by a biased sequence search method. Proteins. 2006 Aug 1; 64(2):444-56.
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        53. Foulkes JE, Prabu-Jeyabalan M, Cooper D, Henderson GJ, Harris J, Swanstrom R, Schiffer CA. Role of invariant Thr80 in human immunodeficiency virus type 1 protease structure, function, and viral infectivity. J Virol. 2006 Jul; 80(14):6906-16.
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        54. Prabu-Jeyabalan M, Nalivaika EA, Romano K, Schiffer CA. Mechanism of substrate recognition by drug-resistant human immunodeficiency virus type 1 protease variants revealed by a novel structural intermediate. J Virol. 2006 Apr; 80(7):3607-16.
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        55. Prabu-Jeyabalan M, King NM, Nalivaika EA, Heilek-Snyder G, Cammack N, Schiffer CA. Substrate envelope and drug resistance: crystal structure of RO1 in complex with wild-type human immunodeficiency virus type 1 protease. Antimicrob Agents Chemother. 2006 Apr; 50(4):1518-21.
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        56. Kolli M, Lastere S, Schiffer CA. Co-evolution of nelfinavir-resistant HIV-1 protease and the p1-p6 substrate. Virology. 2006 Apr 10; 347(2):405-9.
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        57. Liu F, Wagner S, Campbell RB, Nickerson JA, Schiffer CA, Ross AH. PTEN enters the nucleus by diffusion. J Cell Biochem. 2005 Oct 1; 96(2):221-34.
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        58. Surleraux DL, Tahri A, Verschueren WG, Pille GM, de Kock HA, Jonckers TH, Peeters A, De Meyer S, Azijn H, Pauwels R, de Bethune MP, King NM, Prabu-Jeyabalan M, Schiffer CA, Wigerinck PB. Discovery and selection of TMC114, a next generation HIV-1 protease inhibitor. J Med Chem. 2005 Mar 24; 48(6):1813-22.
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        59. Surleraux DL, de Kock HA, Verschueren WG, Pille GM, Maes LJ, Peeters A, Vendeville S, De Meyer S, Azijn H, Pauwels R, de Bethune MP, King NM, Prabu-Jeyabalan M, Schiffer CA, Wigerinck PB. Design of HIV-1 protease inhibitors active on multidrug-resistant virus. J Med Chem. 2005 Mar 24; 48(6):1965-73.
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        60. Johnston E, Winters MA, Rhee SY, Merigan TC, Schiffer CA, Shafer RW. Association of a novel human immunodeficiency virus type 1 protease substrate cleft mutation, L23I, with protease inhibitor therapy and in vitro drug resistance. Antimicrob Agents Chemother. 2004 Dec; 48(12):4864-8.
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        61. King NM, Prabu-Jeyabalan M, Nalivaika EA, Wigerinck P, de Béthune MP, Schiffer CA. Structural and thermodynamic basis for the binding of TMC114, a next-generation human immunodeficiency virus type 1 protease inhibitor. J Virol. 2004 Nov; 78(21):12012-21.
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        62. Prabu-Jeyabalan M, Nalivaika EA, King NM, Schiffer CA. Structural basis for coevolution of a human immunodeficiency virus type 1 nucleocapsid-p1 cleavage site with a V82A drug-resistant mutation in viral protease. J Virol. 2004 Nov; 78(22):12446-54.
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        63. King NM, Prabu-Jeyabalan M, Nalivaika EA, Schiffer CA. Combating susceptibility to drug resistance: lessons from HIV-1 protease. Chem Biol. 2004 Oct; 11(10):1333-8.
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        64. Hoffman NG, Schiffer CA, Swanstrom R. Covariation of amino acid positions in HIV-1 protease. Virology. 2003 Sep 30; 314(2):536-48.
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        65. Kurt N, Haliloglu T, Schiffer CA. Structure-based prediction of potential binding and nonbinding peptides to HIV-1 protease. Biophys J. 2003 Aug; 85(2):853-63.
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        66. Kurt N, Scott WR, Schiffer CA, Haliloglu T. Cooperative fluctuations of unliganded and substrate-bound HIV-1 protease: a structure-based analysis on a variety of conformations from crystallography and molecular dynamics simulations. Proteins. 2003 May 15; 51(3):409-22.
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        67. Wu TD, Schiffer CA, Gonzales MJ, Taylor J, Kantor R, Chou S, Israelski D, Zolopa AR, Fessel WJ, Shafer RW. Mutation patterns and structural correlates in human immunodeficiency virus type 1 protease following different protease inhibitor treatments. J Virol. 2003 Apr; 77(8):4836-47.
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        68. Prabu-Jeyabalan M, Nalivaika EA, King NM, Schiffer CA. Viability of a drug-resistant human immunodeficiency virus type 1 protease variant: structural insights for better antiviral therapy. J Virol. 2003 Jan; 77(2):1306-15.
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        69. Schiffer C, Hermans J. Promise of advances in simulation methods for protein crystallography: implicit solvent models, time-averaging refinement, and quantum mechanical modeling. Methods Enzymol. 2003; 374:412-61.
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        70. Schonhoff CM, Daou MC, Jones SN, Schiffer CA, Ross AH. Nitric oxide-mediated inhibition of Hdm2-p53 binding. Biochemistry. 2002 Nov 19; 41(46):13570-4.
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        71. Pettit SC, Henderson GJ, Schiffer CA, Swanstrom R. Replacement of the P1 amino acid of human immunodeficiency virus type 1 Gag processing sites can inhibit or enhance the rate of cleavage by the viral protease. J Virol. 2002 Oct; 76(20):10226-33.
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        72. Liu H, Radhakrishnan P, Magoun L, Prabu M, Campellone KG, Savage P, He F, Schiffer CA, Leong JM. Point mutants of EHEC intimin that diminish Tir recognition and actin pedestal formation highlight a putative Tir binding pocket. Mol Microbiol. 2002 Sep; 45(6):1557-73.
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        73. Prabu-Jeyabalan M, Nalivaika E, Schiffer CA. Substrate shape determines specificity of recognition for HIV-1 protease: analysis of crystal structures of six substrate complexes. Structure. 2002 Mar; 10(3):369-81.
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        74. Schiffer C, Ultsch M, Walsh S, Somers W, de Vos AM, Kossiakoff A. Structure of a phage display-derived variant of human growth hormone complexed to two copies of the extracellular domain of its receptor: evidence for strong structural coupling between receptor binding sites. J Mol Biol. 2002 Feb 15; 316(2):277-89.
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        75. King NM, Melnick L, Prabu-Jeyabalan M, Nalivaika EA, Yang SS, Gao Y, Nie X, Zepp C, Heefner DL, Schiffer CA. Lack of synergy for inhibitors targeting a multi-drug-resistant HIV-1 protease. Protein Sci. 2002 Feb; 11(2):418-29.
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        76. Bakri Y, Schiffer C, Zennou V, Charneau P, Kahn E, Benjouad A, Gluckman JC, Canque B. The maturation of dendritic cells results in postintegration inhibition of HIV-1 replication. J Immunol. 2001 Mar 15; 166(6):3780-8.
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        77. Scott WR, Schiffer CA. Curling of flap tips in HIV-1 protease as a mechanism for substrate entry and tolerance of drug resistance. Structure. 2000 Dec 15; 8(12):1259-65.
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        78. Prabu-Jeyabalan M, Nalivaika E, Schiffer CA. How does a symmetric dimer recognize an asymmetric substrate? A substrate complex of HIV-1 protease. J Mol Biol. 2000 Sep 1; 301(5):1207-20.
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        79. Hensley ML, Peterson B, Silver RT, Larson RA, Schiffer CA, Szatrowski TP. Risk factors for severe neuropsychiatric toxicity in patients receiving interferon alfa-2b and low-dose cytarabine for chronic myelogenous leukemia: analysis of Cancer and Leukemia Group B 9013. J Clin Oncol. 2000 Mar; 18(6):1301-8.
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        80. Schiffer CA, van Gunsteren WF. Accessibility and order of water sites in and around proteins: A crystallographic time-averaging study. Proteins. 1999 Sep 1; 36(4):501-11.
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        81. Kornblith AB, Herndon JE, Zuckerman E, Cella DF, Cherin E, Wolchok S, Weiss RB, Diehl LF, Henderson E, Cooper MR, Schiffer C, Canellos GP, Mayer RJ, Silver RT, Schilling A, Peterson BA, Greenberg D, Holland JC. Comparison of psychosocial adaptation of advanced stage Hodgkin's disease and acute leukemia survivors. Cancer and Leukemia Group B. Ann Oncol. 1998 Mar; 9(3):297-306.
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        82. Peng JW, Schiffer CA, Xu P, van Gunsteren WF, Ernst RR. Investigations of peptide hydration using NMR and molecular dynamics simulations: A study of effects of water on the conformation and dynamics of antamanide. J Biomol NMR. 1996 Dec; 8(4):453-76.
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        83. Schiffer CA, van Gunsteren WF. Structural stability of disulfide mutants of basic pancreatic trypsin inhibitor: a molecular dynamics study. Proteins. 1996 Sep; 26(1):66-71.
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        84. Schiffer CA, Dötsch V. The role of protein-solvent interactions in protein unfolding. Curr Opin Biotechnol. 1996 Aug; 7(4):428-32.
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        85. Schiffer CA, Clifton IJ, Davisson VJ, Santi DV, Stroud RM. Crystal structure of human thymidylate synthase: a structural mechanism for guiding substrates into the active site. Biochemistry. 1995 Dec 19; 34(50):16279-87.
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        86. Schiffer CA, Dötsch V, Wüthrich K, van Gunsteren WF. Exploring the role of the solvent in the denaturation of a protein: a molecular dynamics study of the DNA binding domain of the 434 repressor. Biochemistry. 1995 Nov 21; 34(46):15057-67.
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        87. Schiffer CA, Gros P, van Gunsteren WF. Time-averaging crystallographic refinement: possibilities and limitations using alpha-cyclodextrin as a test system. Acta Crystallogr D Biol Crystallogr. 1995 Jan 1; 51(Pt 1):85-92.
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        88. Schiffer CA, Huber R, Wüthrich K, van Gunsteren WF. Simultaneous refinement of the structure of BPTI against NMR data measured in solution and X-ray diffraction data measured in single crystals. J Mol Biol. 1994 Aug 26; 241(4):588-99.
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        89. Greene PJ, Yu PL, Zhao J, Schiffer CA, Santi D. Expression, purification, and characterization of thymidylate synthase from Lactococcus lactis. Protein Sci. 1994 Jul; 3(7):1114-6.
          View in: PubMed
        90. Neubauer A, Dodge RK, George SL, Davey FR, Silver RT, Schiffer CA, Mayer RJ, Ball ED, Wurster-Hill D, Bloomfield CD, et al. Prognostic importance of mutations in the ras proto-oncogenes in de novo acute myeloid leukemia. Blood. 1994 Mar 15; 83(6):1603-11.
          View in: PubMed
        91. van Gunsteren WF, Brunne RM, Gros P, van Schaik RC, Schiffer CA, Torda AE. Accounting for molecular mobility in structure determination based on nuclear magnetic resonance spectroscopic and X-ray diffraction data. Methods Enzymol. 1994; 239:619-54.
          View in: PubMed
        92. Sandler DP, Shore DL, Anderson JR, Davey FR, Arthur D, Mayer RJ, Silver RT, Weiss RB, Moore JO, Schiffer CA, et al. Cigarette smoking and risk of acute leukemia: associations with morphology and cytogenetic abnormalities in bone marrow. J Natl Cancer Inst. 1993 Dec 15; 85(24):1994-2003.
          View in: PubMed
        93. Ozer H, George SL, Schiffer CA, Rao K, Rao PN, Wurster-Hill DH, Arthur DD, Powell B, Gottlieb A, Peterson BA, Rai K, Testa JR, LeBeau M, Tantravahi R, Bloomfield CD. Prolonged subcutaneous administration of recombinant alpha 2b interferon in patients with previously untreated Philadelphia chromosome-positive chronic-phase chronic myelogenous leukemia: effect on remission duration and survival: Cancer and Leukemia Group B study 8583. Blood. 1993 Nov 15; 82(10):2975-84.
          View in: PubMed
        94. Schiffer CA, Caldwell JW, Stroud RM, Kollman PA. Inclusion of solvation free energy with molecular mechanics energy: alanyl dipeptide as a test case. Protein Sci. 1992 Mar; 1(3):396-400.
          View in: PubMed
        95. Schiffer CA, Davisson VJ, Santi DV, Stroud RM. Crystallization of human thymidylate synthase. J Mol Biol. 1991 May 20; 219(2):161-3.
          View in: PubMed
        96. Schiffer CA, Caldwell JW, Kollman PA, Stroud RM. Prediction of homologous protein structures based on conformational searches and energetics. Proteins. 1990; 8(1):30-43.
          View in: PubMed
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