1fax
From Proteopedia
| Line 4: | Line 4: | ||
|PDB= 1fax |SIZE=350|CAPTION= <scene name='initialview01'>1fax</scene>, resolution 3.0Å | |PDB= 1fax |SIZE=350|CAPTION= <scene name='initialview01'>1fax</scene>, resolution 3.0Å | ||
|SITE= <scene name='pdbsite=CAT:Catalytic+Center+Of+SER+Protease'>CAT</scene> | |SITE= <scene name='pdbsite=CAT:Catalytic+Center+Of+SER+Protease'>CAT</scene> | ||
| - | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene> | + | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DX9:(+)-2-[4-[((S)-1-ACETIMIDOYL-3-PYRRODINYL)OXY]-3-(7-AMIDINO-2-NAPTHYL)PROPIONIC+ACID'>DX9</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Coagulation_factor_Xa Coagulation factor Xa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.6 3.4.21.6] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Coagulation_factor_Xa Coagulation factor Xa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.6 3.4.21.6] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1fax FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fax OCA], [http://www.ebi.ac.uk/pdbsum/1fax PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1fax RCSB]</span> | ||
}} | }} | ||
| Line 14: | Line 17: | ||
==Overview== | ==Overview== | ||
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. | 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. | ||
| - | |||
| - | ==Disease== | ||
| - | Known disease associated with this structure: Factor X deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=227600 227600]] | ||
==About this Structure== | ==About this Structure== | ||
| Line 28: | Line 28: | ||
[[Category: Brandstetter, H.]] | [[Category: Brandstetter, H.]] | ||
[[Category: Engh, R A.]] | [[Category: Engh, R A.]] | ||
| - | [[Category: CA]] | ||
| - | [[Category: DX9]] | ||
[[Category: blood coagulation factor]] | [[Category: blood coagulation factor]] | ||
[[Category: calcium-binding]] | [[Category: calcium-binding]] | ||
| Line 38: | Line 36: | ||
[[Category: serine protease]] | [[Category: serine protease]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:19:20 2008'' |
Revision as of 17:19, 30 March 2008
| |||||||
| , resolution 3.0Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | , | ||||||
| Activity: | Coagulation factor Xa, with EC number 3.4.21.6 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
COAGULATION FACTOR XA INHIBITOR COMPLEX
Overview
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.
About this Structure
1FAX is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
X-ray structure of active site-inhibited clotting factor Xa. Implications for drug design and substrate recognition., Brandstetter H, Kuhne A, Bode W, Huber R, von der Saal W, Wirthensohn K, Engh RA, J Biol Chem. 1996 Nov 22;271(47):29988-92. PMID:8939944
Page seeded by OCA on Sun Mar 30 20:19:20 2008
