Radzicka, A. & Wolfenden, R. Rates of uncatalyzed peptide bond hydrolysis in neutral solution and the transition state affinities of proteases. J. Am. Chem. Soc. 118, 6105\u20136109 (1996).<\/p>\n
Article<\/a>\u00a0 Dyer, R. P. & Weiss, G. A. Making the cut with protease engineering. Cell Chem. Biol. 29, 177\u2013190 (2022).<\/p>\n Article<\/a>\u00a0 Otto, H.-H. & Schirmeister, T. Cysteine proteases and their inhibitors. Chem. Rev. 97, 133\u2013172 (1997).<\/p>\n Article<\/a>\u00a0 Carter, P. & Wells, J. A. Dissecting the catalytic triad of a serine protease. Nature 332, 564\u2013568 (1988.<\/p>\n Article<\/a>\u00a0 M\u00e9nard, R. et al. Modification of the electrostatic environment is tolerated in the oxyanion hole of the cysteine protease papain. Biochemistry 34, 464\u2013471 (1995).<\/p>\n Article<\/a>\u00a0 Verma, S., Dixit, R. & Pandey, K. C. Cysteine proteases: modes of activation and future prospects as pharmacological targets. Front. Pharmacol. 7, 107 (2016).<\/p>\n Article<\/a>\u00a0 Lauko, A. et al. Computational design of serine hydrolases. Science 388, eadu2454 (2025).<\/p>\n Article<\/a>\u00a0 Kim, D. et al. Computational design of metallohydrolases. Nature 649, 246\u2013253 (2026).<\/p>\n Ahern, W. et al. Atom-level enzyme active site scaffolding using RFdiffusion2. Nat. Methods 23, 96\u2013105 (2026).<\/p>\n Article<\/a>\u00a0 Bauer, M. S. et al. De novo design of phospho-tyrosine peptide binders. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/2025.09.29.678898<\/a> (2025).<\/p>\n Mossessova, E. & Lima, C. D. Ulp1-SUMO crystal structure and genetic analysis reveal conserved interactions and a regulatory element essential for cell growth in yeast. Mol. Cell 5, 865\u2013876 (2000).<\/p>\n Article<\/a>\u00a0 Dauparas, J. et al. Robust deep learning-based protein sequence design using ProteinMPNN. Science 378, 49\u201356 (2022).<\/p>\n Article<\/a>\u00a0 Abramson, J. et al. Accurate structure prediction of biomolecular interactions with AlphaFold 3. Nature 630, 493\u2013500 (2024).<\/p>\n Article<\/a>\u00a0 Bindels, D. S. et al. mScarlet: a bright monomeric red fluorescent protein for cellular imaging. Nat. Methods 14, 53\u201356 (2017).<\/p>\n Article<\/a>\u00a0 Matayoshi, E. D., Wang, G. T., Krafft, G. A. & Erickson, J. Novel fluorogenic substrates for assaying retroviral proteases by resonance energy transfer. Science 247, 954\u2013958 (1990).<\/p>\n Article<\/a>\u00a0 Hofer, F., Kraml, J., Kahler, U., Kamenik, A. S. & Liedl, K. R. Catalytic site pKa values of aspartic, cysteine, and Serine proteases: Constant pH MD simulations. J. Chem. Inf. Model. 60, 3030\u20133042 (2020).<\/p>\n Article<\/a>\u00a0 Zhai, X. & Meek, T. D. Catalytic mechanism of cruzain from Trypanosoma cruzi as determined from solvent kinetic isotope effects of steady-state and pre-steady-state kinetics. Biochemistry 57, 3176\u20133190 (2018).<\/p>\n Article<\/a>\u00a0 Daniel, R. M. & Danson, M. J. A new understanding of how temperature affects the catalytic activity of enzymes. Trends Biochem. Sci 35, 584\u2013591 (2010).<\/p>\n Article<\/a>\u00a0 Xu, Z. et al. Molecular basis of the redox regulation of SUMO proteases: a protective mechanism of intermolecular disulfide linkage against irreversible sulfhydryl oxidation. FASEB J. 22, 127\u2013137 (2008).<\/p>\n Article<\/a>\u00a0 van Kempen, M. et al. Fast and accurate protein structure search with Foldseek. Nat. Biotechnol. 42, 243\u2013246 (2024).<\/p>\n Article<\/a>\u00a0 Zhang, Y. & Skolnick, J. Scoring function for automated assessment of protein structure template quality. Proteins 57, 702\u2013710 (2004).<\/p>\n Article<\/a>\u00a0 Anishchenko, I. et al. Modeling protein-small molecule conformational ensembles with PLACER. Proc. Natl Acad. Sci. USA 122, e2427161122 (2025).<\/p>\n Article<\/a>\u00a0 LaLonde, J. M. et al. Use of papain as a model for the structure-based design of cathepsin K inhibitors: crystal structures of two papain-inhibitor complexes demonstrate binding to S\u2032-subsites. J. Med. Chem. 41, 4567\u20134576 (1998).<\/p>\n Article<\/a>\u00a0 Tsuge, H. et al. Inhibition mechanism of cathepsin L-specific inhibitors based on the crystal structure of papain-CLIK148 complex. Biochem. Biophys. Res. Commun. 266, 411\u2013416 (1999).<\/p>\n Article<\/a>\u00a0 Moldoveanu, T., Campbell, R. L., Cuerrier, D. & Davies, P. L. Crystal structures of calpain-E64 and -leupeptin inhibitor complexes reveal mobile loops gating the active site. J. Mol. Biol. 343, 1313\u20131326 (2004).<\/p>\n Article<\/a>\u00a0 Falke, S. et al. Structural elucidation and antiviral activity of covalent cathepsin L inhibitors. J. Med. Chem. 67, 7048\u20137067 (2024).<\/p>\n Article<\/a>\u00a0 Yamamoto, A. et al. Structural basis for development of cathepsin B-specific noncovalent-type inhibitor: crystal structure of cathepsin B-E64c complex. Biochim. Biophys. Acta 1597, 244\u2013251 (2002).<\/p>\n Article<\/a>\u00a0 Pauly, T. A. et al. Specificity determinants of human cathepsin s revealed by crystal structures of complexes. Biochemistry 42, 3203\u20133213 (2003).<\/p>\n Article<\/a>\u00a0 Huang, L., Brinen, L. S. & Ellman, J. A. Crystal structures of reversible ketone-Based inhibitors of the cysteine protease cruzain. Bioorg. Med. Chem. 11, 21\u201329 (2003).<\/p>\n Article<\/a>\u00a0 Kapust, R. B. et al. Tobacco etch virus protease: mechanism of autolysis and rational design of stable mutants with wild-type catalytic proficiency. Protein Eng. 14, 993\u20131000 (2001).<\/p>\n Article<\/a>\u00a0 Kenneson, J. R. et al. Exploring possible drug-resistant variants of SARS-CoV-2 main protease (Mpro) with noncovalent preclinical candidate, Mpro61. ACS Bio Med Chem Au 5, 215\u2013226 (2025).<\/p>\n Article<\/a>\u00a0 Mei, M. et al. A combinatorial strategy for HRV 3C protease engineering to achieve the N-terminal free cleavage. Int. J. Biol. Macromol. 265, 131066 (2024).<\/p>\n Article<\/a>\u00a0 Pearlman, D. A. et al. AMBER, a package of computer programs for applying molecular mechanics, normal mode analysis, molecular dynamics and free energy calculations to simulate the structural and energetic properties of molecules. Comput. Phys. Commun. 91, 1\u201341 (1995).<\/p>\n Article<\/a>\u00a0 Shaffer, J. M. & Greenwald, I. SALSA, a genetically encoded biosensor for spatiotemporal quantification of Notch signal transduction in vivo. Dev. Cell 57, 930\u2013944.e6 (2022).<\/p>\n Gao, X. J., Chong, L. S., Kim, M. S. & Elowitz, M. B. Programmable protein circuits in living cells. Science 361, 1252\u20131258 (2018).<\/p>\n Article<\/a>\u00a0 Roybal, K. T. et al. Engineering T cells with customized therapeutic response programs using synthetic Notch receptors. Cell 167, 419\u2013432 (2016).<\/p>\n Article<\/a>\u00a0 Barnea, G. et al. The genetic design of signaling cascades to record receptor activation. Proc. Natl Acad. Sci. USA 105, 64\u201369 (2008).<\/p>\n Article<\/a>\u00a0 Coukos, R. et al. An engineered transcriptional reporter of protein localization identifies regulators of mitochondrial and ER membrane protein trafficking in high-throughput CRISPRi screens. eLife 10, e69142 (2021).<\/p>\n Article<\/a>\u00a0 Novinec, M. & Lenar\u010di\u010d, B. Papain-like peptidases: structure, function, and evolution. Biomol. Concepts 4, 287\u2013308 (2013).<\/p>\n Article<\/a>\u00a0 Hekkelman, M. L., Salmoral, D. \u00c1, Perrakis, A. & Joosten, R. P. DSSP 4: FAIR annotation of protein secondary structure. Protein Sci. 34, e70208 (2025).<\/p>\n Article<\/a>\u00a0 Bennett, N. R. et al. Improving de novo protein binder design with deep learning. Nat. Commun. 14, 2625 (2023).<\/p>\n Article<\/a>\u00a0 Kuo, C.-J., Chi, Y.-H., Hsu, J. T.-A. & Liang, P.-H. Characterization of SARS main protease and inhibitor assay using a fluorogenic substrate. Biochem. Biophys. Res. Commun. 318, 862\u2013867 (2004).<\/p>\n ADS<\/a>\u00a0 Kabsch, W. Integration, scaling, space-group assignment and post-refinement. Acta Crystallogr. D 66, 133\u2013144 (2010).<\/p>\n Article<\/a>\u00a0 Winn, M. D. et al. Overview of the CCP4 suite and current developments. Acta Crystallogr. D 67, 235\u2013242 (2011).<\/p>\n Article<\/a>\u00a0 McCoy, A. J. et al. Phaser crystallographic software. J. Appl. Crystallogr. 40, 658\u2013674 (2007).<\/p>\n Article<\/a>\u00a0 Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. In International Tables for Crystallography 539\u2013547 (International Union of Crystallography, 2012).<\/p>\n Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D 60, 2126\u20132132 (2004).<\/p>\n Article<\/a>\u00a0 Williams, C. J. et al. MolProbity: more and better reference data for improved all-atom structure validation. Protein Sci. 27, 293\u2013315 (2018).<\/p>\n Article<\/a>\u00a0
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