1zhm

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:1zhm.gif|left|200px]]
+
{{Seed}}
 +
[[Image:1zhm.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_1zhm| PDB=1zhm | SCENE= }}
{{STRUCTURE_1zhm| PDB=1zhm | SCENE= }}
-
'''Crystal Structure of the Catalytic Domain of the Coagulation Factor XIa in Complex with Benzamidine (S434A-T475A-K437 Mutant)'''
+
===Crystal Structure of the Catalytic Domain of the Coagulation Factor XIa in Complex with Benzamidine (S434A-T475A-K437 Mutant)===
-
==Overview==
+
<!--
-
Activated factor XI (FXIa) is a key enzyme in the amplification phase of the blood-coagulation cascade. Thus, a selective FXIa inhibitor may have lesser bleeding liabilities and provide a safe alternative for antithrombosis therapy to available drugs on the market. In a previous report, the crystal structures of the catalytic domain of FXIa (rhFXI(370-607)) in complex with various ecotin mutants have been described. However, ecotin forms a matrix-like interaction with rhFXI(370-607) and is impossible to displace with small-molecule inhibitors; ecotin crystals are therefore not suitable for iterative structure-based ligand design. In addition, rhFXI(370-607) did not crystallize in the presence of small-molecule ligands. In order to obtain the crystal structure of rhFXI(370-607) with a weak small-molecule ligand, namely benzamidine, several rounds of surface-residue mutation were implemented to promote crystal formation of rhFXI(370-607). A quadruple mutant of rhFXI(370-607) (rhFXI(370-607)-S434A,T475A,C482S,K437A) readily crystallized in the presence of benzamidine. The benzamidine in the preformed crystals was easily exchanged with other FXIa small-molecule inhibitors. These crystals have facilitated the structure-based design of small-molecule FXIa inhibitors.
+
The line below this paragraph, {{ABSTRACT_PUBMED_16204896}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 16204896 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_16204896}}
==Disease==
==Disease==
Line 34: Line 38:
[[Category: Benzamidine]]
[[Category: Benzamidine]]
[[Category: Factor xi]]
[[Category: Factor xi]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 17:38:02 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 22:01:46 2008''

Revision as of 19:01, 28 July 2008

Image:1zhm.png

Template:STRUCTURE 1zhm

Contents

Crystal Structure of the Catalytic Domain of the Coagulation Factor XIa in Complex with Benzamidine (S434A-T475A-K437 Mutant)

Template:ABSTRACT PUBMED 16204896

Disease

Known disease associated with this structure: Factor XI deficiency, autosomal dominant OMIM:[264900], Factor XI deficiency, autosomal recessive OMIM:[264900]

About this Structure

1ZHM is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Mutation of surface residues to promote crystallization of activated factor XI as a complex with benzamidine: an essential step for the iterative structure-based design of factor XI inhibitors., Jin L, Pandey P, Babine RE, Weaver DT, Abdel-Meguid SS, Strickler JE, Acta Crystallogr D Biol Crystallogr. 2005 Oct;61(Pt 10):1418-25. Epub 2005, Sep 28. PMID:16204896

Page seeded by OCA on Mon Jul 28 22:01:46 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1zhm"
Personal tools