2J4I

CRYSTAL STRUCTURE OF A HUMAN FACTOR XA INHIBITOR COMPLEX

Summary for 2J4I

• Entry DOI: 10.2210/pdb2j4i/pdb
• Related: 1C5M 1EZQ 1F0R 1F0S 1FAX 1FJS 1FXY 1G2L 1G2M 1HCG 1IOE 1IQE 1IQF 1IQG 1IQH 1IQI 1IQJ 1IQK 1IQL 1IQM 1IQN 1KSN 1KYE 1LPG 1LPK 1LPZ 1LQD 1MQ5 1MQ6 1MSX 1NFU 1NFW 1NFX 1NFY 1NL8 1P0S 1V3X 1WU1 1XKA 1XKB 1Z6E 2BMG 2BOH 2BOK 2BQ6 2BQ7 2BQW 2CJI 2FZZ 2GD4 2J2U 2J34 2J38
• Descriptor: COAGULATION FACTOR X, 1-PYRROLIDINEACETAMIDE, 3-[[(6-CHLORO-2-NAPHTHALENYL)SULFONYL]AMINO]-ALPHA-METHYL-N-(1-METHYLETHYL)-N-[2-[(METHYLSULFONYL)AMINO]ETHYL]-2-OXO-, (ALPHAS,3S)-, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: blood coagulation, calcium, egf-like domain, gamma-carboxyglutamic acid, glycoprotein, hydrolase, hydroxylation, polymorphism, protease, serine protease, zymogen, complex
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Secreted: P00742 P00742
• Total number of polymer chains: 2
• Total formula weight: 44360.57

Authors

Young, R.J.,Campbell, M.,Borthwick, A.D.,Brown, D.,Chan, C.,Convery, M.A.,Crowe, M.C.,Dayal, S.,Diallo, H.,Kelly, H.A.,Paul King, N.,Kleanthous, S.,Kurtis, C.L.,Mason, A.M.,Mordaunt, J.E.,Patel, C.,Pateman, A.J.,Senger, S.,Shah, G.P.,Smith, P.W.,Watson, N.S.,Weston, H.E.,Zhou, P. (deposition date: 2006-08-31, release date: 2006-09-27, Last modification date: 2024-11-13)

Primary citation

Young, R.J.,Campbell, M.,Borthwick, A.D.,Brown, D.,Burns-Kurtis, C.L.,Chan, C.,Convery, M.A.,Crowe, M.C.,Dayal, S.,Diallo, H.,Kelly, H.A.,Paul King, N.,Kleanthous, S.,Mason, A.M.,Mordaunt, J.E.,Patel, C.,Pateman, A.J.,Senger, S.,Shah, G.P.,Smith, P.W.,Watson, N.S.,Weston, H.E.,Zhou, P.
Structure- and Property-Based Design of Factor Xa Inhibitors: Pyrrolidin-2-Ones with Acyclic Alanyl Amides as P4 Motifs.
Bioorg.Med.Chem.Lett., 16:5953-, 2006

PubMed Abstract: Structure-based drug design was exploited in the synthesis of 3-(6-chloronaphth-2-ylsulfonyl)aminopyrrolidin-2-one-based factor Xa (fXa) inhibitors, incorporating an alanylamide P4 group with acyclic tertiary amide termini. Optimized hydrophobic contacts of one amide substituent in P4 were complemented by hydrophobicity-modulating features in the second, producing potent fXa inhibitors including examples with excellent anticoagulant properties.

PubMed: 16982190
DOI: 10.1016/J.BMCL.2006.09.001

Experimental method

X-RAY DIFFRACTION (1.8 Å)