1FAX

COAGULATION FACTOR XA INHIBITOR COMPLEX

Summary for 1FAX

• Entry DOI: 10.2210/pdb1fax/pdb
• Descriptor: FACTOR XA, CALCIUM ION, (2S)-3-(7-carbamimidoylnaphthalen-2-yl)-2-[4-({(3R)-1-[(1Z)-ethanimidoyl]pyrrolidin-3-yl}oxy)phenyl]propanoic acid, ... (4 entities in total)
• Functional Keywords: glycoprotein, hydrolase, serine protease, plasma, blood coagulation factor, gamma-carboxyglutamic acid, calcium-binding, coagulation factor
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P00742 P00742
• Total number of polymer chains: 2
• Total formula weight: 39410.80

Authors

Brandstetter, H.,Engh, R.A. (deposition date: 1996-08-23, release date: 1997-10-29, Last modification date: 2024-10-16)

Primary citation

Brandstetter, H.,Kuhne, A.,Bode, W.,Huber, R.,von der Saal, W.,Wirthensohn, K.,Engh, R.A.
X-ray structure of active site-inhibited clotting factor Xa. Implications for drug design and substrate recognition.
J.Biol.Chem., 271:29988-29992, 1996

PubMed Abstract: The 3.0-A resolution x-ray structure of human des-Gla-coagulation factor Xa (fXa) has been determined in complex with the synthetic inhibitor DX-9065a. The binding geometry is characterized primarily by two interaction sites: the naphthamidine group is fixed in the S1 pocket by a typical salt bridge to Asp-189, while the pyrrolidine ring binds in the unique aryl-binding site (S4) of fXa. Unlike the large majority of inhibitor complexes with serine proteinases, Gly-216 (S3) does not contribute to hydrogen bond formation. In contrast to typical thrombin binding modes, the S2 site of fXa cannot be used by DX-9065a since it is blocked by Tyr-99, and the aryl-binding site (S4) of fXa is lined by carbonyl oxygen atoms that can accommodate positive charges. This has implications for natural substrate recognition as well as for drug design.

PubMed: 8939944
DOI: 10.1074/jbc.271.47.29988

Experimental method

X-RAY DIFFRACTION (3 Å)