5F02

CATHEPSIN L IN COMPLEX WITH (2S,4R)-4-(2-Chloro-4-methoxy-benzenesulfonyl)-1-[3-(5-chloro-pyridin-2-yl)-azetidine-3-carbonyl]-pyrrolidine-2-carboxylic acid (1-cyano-cyclopropyl)-amide

Summary for 5F02

• Entry DOI: 10.2210/pdb5f02/pdb
• Descriptor: Cathepsin L1, GLYCEROL, (2~{S},4~{R})-4-[(2-chloranyl-4-methoxy-phenyl)-bis(oxidanyl)-$l^{4}-sulfanyl]-1-[3-(5-chloranylpyridin-2-yl)azetidin-3-yl]carbonyl-~{N}-[1-(iminomethyl)cyclopropyl]pyrrolidine-2-carboxamide, ... (4 entities in total)
• Functional Keywords: protease inhibitor, hydrolase-hydrolase inhibitor complex, hydrolase
• Biological source: Homo sapiens (Human)
• Cellular location: Lysosome: P07711
• Total number of polymer chains: 1
• Total formula weight: 24866.29

Authors

Banner, D.,Benz, J.,Stihle, M.,Kuglstatter, A. (deposition date: 2015-11-27, release date: 2016-02-24, Last modification date: 2024-10-23)

Primary citation

Kuhn, B.,Guba, W.,Hert, J.,Banner, D.,Bissantz, C.,Ceccarelli, S.,Haap, W.,Korner, M.,Kuglstatter, A.,Lerner, C.,Mattei, P.,Neidhart, W.,Pinard, E.,Rudolph, M.G.,Schulz-Gasch, T.,Woltering, T.,Stahl, M.
A Real-World Perspective on Molecular Design.
J.Med.Chem., 59:4087-4102, 2016

PubMed Abstract: We present a series of small molecule drug discovery case studies where computational methods were prospectively employed to impact Roche research projects, with the aim of highlighting those methods that provide real added value. Our brief accounts encompass a broad range of methods and techniques applied to a variety of enzymes and receptors. Most of these are based on judicious application of knowledge about molecular conformations and interactions: filling of lipophilic pockets to gain affinity or selectivity, addition of polar substituents, scaffold hopping, transfer of SAR, conformation analysis, and molecular overlays. A case study of sequence-driven focused screening is presented to illustrate how appropriate preprocessing of information enables effective exploitation of prior knowledge. We conclude that qualitative statements enabling chemists to focus on promising regions of chemical space are often more impactful than quantitative prediction.

PubMed: 26878596
DOI: 10.1021/acs.jmedchem.5b01875

Experimental method

X-RAY DIFFRACTION (1.43 Å)