1nfw: Difference between revisions
New page: left|200px<br /> <applet load="1nfw" size="450" color="white" frame="true" align="right" spinBox="true" caption="1nfw, resolution 2.1Å" /> '''CRYSTAL STRUCTURE OF... |
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'''CRYSTAL STRUCTURE OF HUMAN COAGULATION FACTOR XA COMPLEXED WITH RPR209685'''<br /> | '''CRYSTAL STRUCTURE OF HUMAN COAGULATION FACTOR XA COMPLEXED WITH RPR209685'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
1NFW is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CA and RRR as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | 1NFW is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=RRR:'>RRR</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NFW OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: hydrolase]] | [[Category: hydrolase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:28:47 2008'' | ||
Revision as of 17:28, 15 February 2008
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CRYSTAL STRUCTURE OF HUMAN COAGULATION FACTOR XA COMPLEXED WITH RPR209685
OverviewOverview
The structures of the noncovalent complex of human factor Xa (fXa) with, four non-peptide inhibitors containing a central sulfonylpiperazinone, scaffold have been determined to about 2.1 A resolution. Highly potent fXa, inhibitors containing both neutral groups such as chlorobenzothiophene or, chlorothiophene and basic groups such as benzamidine were shown to, interact in the S1 pocket through the neutral group whereas the S4 pocket, is occupied by the basic moiety. The scaffold comprising the sulfonyl keto, piperazine moiety might play a pivotal role in the orientation of, substituents, since there is a strong hydrogen bond between Gly219 of fXa, and the carbonyl oxygen of the piperazine. This unique "reverse" binding, mode is heretofore unreported in fXa and shows that electrostatic, interactions in the S1 subsite are not an absolute requirement to maintain, high affinity. Selectivity against other serine proteases can be readily, explained in light of these structural results. It has opened up new, prospects for designing fXa inhibitors with increased oral, bioavailability.
DiseaseDisease
Known disease associated with this structure: Factor X deficiency OMIM:[227600]
About this StructureAbout this Structure
1NFW is a Protein complex structure of sequences from Homo sapiens with and as ligands. Active as Coagulation factor Xa, with EC number 3.4.21.6 Full crystallographic information is available from OCA.
ReferenceReference
Molecular structures of human factor Xa complexed with ketopiperazine inhibitors: preference for a neutral group in the S1 pocket., Maignan S, Guilloteau JP, Choi-Sledeski YM, Becker MR, Ewing WR, Pauls HW, Spada AP, Mikol V, J Med Chem. 2003 Feb 27;46(5):685-90. PMID:12593649
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