Wells LabUCSF, Depts of Pharmaceutical Chemistry and Cellular and Molecular Pharmacology
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Publications

2011

Zorn J.A., Wille H., Wolan D.W., Wells J.A. (2011) J Am Chem Soc. (in press). "Self-Assembling Small Molecules Form Nanofibrils That Bind Procaspase-3 to Promote Activation"

Gao J. & Wells J.A. (2011) Chem Biol Drug Des (in press). "Identification of Specific Tethered Inhibitors for Caspase-5"

Tang Y., Wells J.A. & Arkin M.R. (2011) J Biol Chem. 286, 34147-34154. "Structural and enzymatic insights into caspase-2 substrate recognition and catalysis"

Crawford E.D. & Wells J.A. (2011) Annu Rev Biochem. Jun 7;80:1055-87. "Caspase substrates and cellular remodeling."

Sadowsky, J., Burlingame, M., Wolan, D., McClendon, C., Jacobson, M., & Wells, J.A. (2011) Proc. Natl. Acad. Sci. USA. Apr 12;108(15):6056-61. "Turning a protein kinase (PDK1) on or off from a single allosteric site via disulfide trapping"

2010

Barkan, D.T., Hostetter, D.R., Mahrus, S., Pieper, U., Wells, J.A., Craik, C.S. & Sali, A. (2010) Bioinformatics 26,1714-22. "Prediction of protease substrates using sequence and structure features"

Zorn, JA, & Wells, JA. (2010) Nat Chem Biol 3, 179-188. "Turning enzymes ON with small molecules"

Perez-Paya, E., Orzaez, M, Mondragon, L, Wolan, D, Wells, JA, Messeguer, A, Vincent, MJ. (2010) Med Res Rev. "Molecules that modulate Apaf-1 activity"

Gray, D.C., Mahrus, S. & Wells. J.A. (2010) Cell 142, 637-646 "Activation of specific apoptotic caspases with an engineered small molecule activated protease"

Agard, N.J, Maltby, D. & Wells, J.A. (2010) Mol. Cell. Proteomics 5, 880-893. "Inflammatory stimuli regulate caspase substrate profiles"

Wildes, D & Wells, J.A. (2010) Proc. Natl. Acad. Sci. USA 107(10), 4561-4566. "Sampling the N-terminal proteome of human blood"

2009

Agard, N. & Wells, J.A. (2009) Curr Opin Chem Biol 13(5-6), 503-509. "Methods for the proteomic identification of protease substrates"

Hardy, J. & Wells, J.A. (2009) Journal of Biological Chemistry 284(38), 26063-26069. "Dissecting an allosteric switch in caspase-7 using chemical and mutational probes"

Wolan DW, Zorn JA, Gray DC, Wells JA. (2009) Science 326, 853-858. “Small-molecule activators of a proenzyme”

Agard NJ, Wells JA. (2009) Curr Opin Chem Biol 13, 503-509. “Methods for the proteomic identification of protease substrates”

Gao J, Sidhu SS, Wells JA. (2009) Proc. Natl. Acad. Sci USA 106, 3071-3076. “Two-state selection of conformation-specific antibodies”

2008

Yoshihara HA, Mahrus S, Wells JA. (2008) Bioorg Med Chem Lett. 18, 6000-6003. “Tags for labeling protein N-termini with subtiligase for proteomics”

Mahrus S, Trinidad JC, Barkan DT, Sali A, Burlingame AL, Wells JA. (2008) Cell 134, 866-876. “Global sequencing of proteolytic cleavage sites in apoptosis by specific labeling of protein N termini”

Datta D, Scheer JM, Romanowski MJ, Wells JA. (2008) J Mol Biol. 381, 1157-1167. “An allosteric circuit in caspase-1”

2007

Wells JA, McClendon CL. (2007) Nature 450, 1001-1009. “Reaching for high-hanging fruit in drug discovery at protein-protein interfaces”

2006

Scheer, J., Romanowski, M. and Wells, J.A. (2006) Proc. Natl. Acad. Sci. USA 103, 7595-7600. "A Common Allosteric Site and Mechanism in Caspases"

2005

Buck, E. and Wells, J.A. (2005) Proc. Natl. Acad. Sci. USA 102, 2719-2724. "Disulfide Trapping to Localize Small Molecule Agonists and Antagonists for the Complement 5a Receptor"

Buck, E., Bourne, H. and Wells, J.A. (2005) J. Biol. Chem 280, 4009-4012. "Site-specific Disulfide Capture of Agonist and Antagonist Peptides to the C5a Receptor"

2004

Hardy, J.A. and Wells, J.A. (2004) Current Opinion in Structural Biology 14, 706-715. "Searching for New Allosteric Sites in Enzymes"

Hardy, J.A., Lam, J., Nguyen, J.T., O’Brien, T and Wells, J.A. (2004) Proc. Natl. Acad. Sci. USA "Discovery of an Allosteric Site in Caspases". 101, 12461-12466.

Erlanson, D.A., Wells, J.A. and Braisted, A.B. (2004) Annu. Rev. Biophys. Biomol Struct. "TETHERING: Fragment-based Drug Discovery". 33, 199-233.

Arkin, M.R. and Wells, J.A. (2004) Nature Rev. Drug Disc. 3, 301-317. "Small Molecule Inhibitors of Protein-Protein Interactions: Progressing Towards the Dream"

Stroud, R.M. and Wells, J.A. (2004) Science STKE, 2004, re7. "Mechanistic Diversity of Cytokine Signaling Across Cell Membranes"

2003

Thanos, C.D., Randal, M., and Wells, J.A. (2003) J. Am. Chem. Soc., 125, 15280-15281. "Potent Small-molecule Binding to a Dynamic Hot-spot on IL-2"

Nguyen, J. and Wells, J.A. (2003) Proc. Natl. Acad. Sci USA, 100, 7533-7538. "Direct Activation of the Apoptosis Machinery as a Mechanism to target Cancer Cells"

Arkin, M.R., Randal, M., DeLano, W., Hyde, J., Loung, T.N., Oslob, J.D., Raphael, D.R., Taylor, L., Wang, J., McDowell, R.S., Wells, J.A., Braisted, A.C. (2003) Proc. Natl. Acad. Sci USA 100, 1603-1608. "Binding of Small Molecules to an Adaptive Protein:Protein Interface"

Selected Earlier Publications

Erlanson, D.A., Braisted, A.C., Raphael, D.R., Randal, M., Stroud, R.M., Gordon, E.M. and Wells, J.A. (2000) Proc. Natl. Acad. Sci. USA 97, 9367-9372. "Site-Directed Ligand Discovery"

DeLano, W.L., Ultsch, M.H., De Vos, A.M. and Wells, J.A. (2000) Science 287, 1279-1283. "Convergent Solutions to Binding at a Protein-Protein Interface"

Atwell, S. and Wells, J.A. (1999) Proc. Natl. Acad. Sci USA 96, 9497-9502. "Selection for Improved Subtiligases by Phage Display"

Ballinger, M.D. and Wells, J.A. (1998) Nature Struct. Biol. 5, 938-940. "Will Any Dimer Do?" News and Views

Clackson, T., Ultsch, M., Wells, J.A. and De Vos, A.A. (1998) J. Mol. Biol. 277, 1111-1128. "Structural and Functional Analysis of the 1:1 Growth Hormone:Receptor Complex Reveals the Molecular Basis for Receptor Affinity"

Wiesmann, C., Fuh, G., Christinger, H.W., Eigenbrot, C., Wells, J.A., De Vos, A.M. (1997) Cell 91, 695-704. "Crystal Structure at 1.7Å resolution of VEGF in Complex with Domain 2 of the Flt-1 Receptor"

Atwell, S., Ultsch, M., De Vos, A.M. and Wells, J.A. (1997) Science 278, 1124-1127 "Structural Plasticity in a Remodeled Protein-Protein Interface"

Ellman, J., Stoddard, B., and Wells, J.A. (1997) Proc. Natl. Acad. Sci. USA 94, 2779-2782. "Combinatorial Thinking in Chemistry and Biology"

Wells, J.A. (1996) Science 273, 449-450. "Hormone Mimicry". Review.

Li, B., Tom, J.Y.K., Oare, D., Yen, R., Fairbrother, W., Wells, J.A., and Cunningham, B.C. (1995) Science 270, 1657-1660. "Minimization of a Polypeptide Hormone"

Wells, J.A. (1995) Biotechnology 13, 647-651. "Structural and Functional Epitopes in the Growth Hormone Receptor Complex"

Clackson, T. and Wells, J.A. (1995) Science 267, 383-386. " A Hot Spot of Binding Energy in a Hormone-Receptor Interface"

Chang, T.K., Jackson, D.Y., Burnier, J.P. and Wells, J.A. (1994) Proc. Natl. Acad. Sci. USA 91, 12544-12548. "Subtiligase: a Tool for Semi-synthesis of Proteins"

Jackson, D.Y., Burnier, J., Quan, C., Stanley, M., Tom, J. and Wells, J.A. (1994) Science 266, 243-247. "A Designed Peptide Ligase for Total Synthesis of Ribonuclease A with Unnatural Catalytic Residues."

Matthews, D.J. and Wells, J.A. (1993) Science 260, 1113-1117. "Substrate Phage: Selection of Protease Substrates by Monovalent Phage Display."

Fuh, G. Cunningham, B.C., Fukunaga, R., Nagata, S., Goeddel, D.V., and Wells, J.A. (1992) Science, 256, 1677-1680. "Rational Design of Potent Antagonists to the Human Growth Hormone Receptor."

Cunningham, B.C., Ultsch, M., DeVos, A.M., Mulkerrin, M.G., Clauser, K.R., Wells, J.A. (1991) Science 254, 821-825. "Dimerization of the Extracellular Domain of the Human Growth Hormone Receptor by a Single Hormone Molecule."

Lowman, H.B., Bass, S., Simpson, N., Wells, J.A. (1991) Biochemistry 30, 10832-10838 "Engineering a Hormone for Improved Receptor binding Affinity by Monovalent Phage Display."

Cunningham, B.C., Mulkerrin, M.G., and Wells, J.A. (1991) Science 253, 545-548, "Dimerization of Human Growth Hormone by Zinc."

Cunningham, B.C., and Wells, J.A. (1991) Proc. Natl. Acad. Sci. USA 88, 3407-3411. "Rational design of receptor specific variants of human growth hormone."

Cunningham, B.C., Bass, S., Fuh, G., and Wells, J.A. (1990) Science 250, 1709-1712 "Zinc mediation of the binding of human growth hormone to the human prolactin receptor."

Cunningham, B.C., Henner, D.J. and Wells, J.A. (1990) Science 247, 1461-1465. "Engineering human prolactin to bind to the human growth hormone receptor."

Cunningham, B.C. and Wells, J.A., (1989) Science 244, 1081-1085. "High-resolution epitope mapping of hGH-receptor interactions by alanine-scanning mutagenesis."

Cunningham, B.C., Jhurani, P., Ng, P. and Wells, J.A., (1989) Science 243, 1330-1336. "Receptor and antibody epitopes in human growth hormone identified by homolog-scanning mutagenesis."

Mitchinson, C. and Wells, J.A. (1989) Biochemistry 28, 4807-4815. "Protein engineering of disulfide bonds in subtilisin."

Wells, J.A. and Estell, D.A. (1988) Trends in Biochem. Sci. 13, 291-297. "Subtilisin - an enzyme designed to be engineered."

Carter, P. and Wells, J.A. (1988) Nature 332, 564-568. "Dissecting the catalytic triad of a serine protease."

Carter, P., and Wells, J.A. (1987) Science 24, 394-399. "Engineering substrate specificity by substrate-assisted catalysis."

Wells, J.A., Cunningham, B.C., Graycar, T.P., and Estell, D.A. (1987). Proc. Natl. Acad. Sci. USA 84, 5167-5171. "Recruitment of substrate specificity properties from one enzyme into a related one by protein engineering."

Wells, J.A., Powers, D.B., Bott, R.R., Graycar, T.P., and Estell, D.A. (1987) Proc. Natl. Acad. Sci. USA 84, 1219-1223. "Designing substrate specificity by protein engineering of electrostatic interactions."

Estell, D.A., Graycar, T.P., Miller, J.V., Powers, D.B., Burnier, J.P., Ng, P.G., and Wells, J.A. (1986) Science 233, 659-663. "Probing steric and hydrophobic effects on enzyme-substrate interactions by protein engineering."

Wells, J.A., Powers, D.B., Bott, R.R., Katz, B.A., Ultsch, M.H., Kossiakoff, A.A., Power, S.D., Adams, R.M., Heyneker, H.H., Cunningham, B.C., Miller, J.V., Graycar, T.P., and Estell, D.A. (1987) in Protein Engineering (A.R. Liss) in press, "Protein engineering of subtilisin."

Wells, J.A. and Powers, D.B. (1986) J. Biol. Chem. 261, 6564-6570. "In vivo formation and stability of engineered disulfide bonds in subtilisin."

Wells, J.A. and Yount, R.G. (1979) Proc. Natl. Acad. Sci. USA 76, 4966-4970. "Active site trapping of nucleotides by crosslinking two sulfhydryls in myosin sub-fragment 1."