Factor Xa
From Proteopedia
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The S1 pocket determines binding selectivity for factor Xa. It is formed by loops in residues 214-220 and 189-195 that are linked by a Cys220-Cys191 disulfide bond. Residues 225-228 form the lower portion of the pocket. | The S1 pocket determines binding selectivity for factor Xa. It is formed by loops in residues 214-220 and 189-195 that are linked by a Cys220-Cys191 disulfide bond. Residues 225-228 form the lower portion of the pocket. | ||
| - | The S2 site of factor Xa is formed by the 90s loop which is positioned adjacent to His57. | + | The S2 site of factor Xa is formed by the 90s loop which is positioned adjacent to His57. Consistent with glycine as the P2 element in prothrombin, S2 is a small, shallow pocket. |
===Activation domain=== | ===Activation domain=== | ||
Revision as of 20:02, 25 April 2010
Contents |
Introduction
Factor X is a vitamin K-dependent glycoprotein that is synthesized in the liver. Zymogen factor X circulates in plasma as a 2 chain molecule composed of a disulfide linked light chain (Mr = 16500) and heavy chain (Mr = 42,000). Factor X is activated to factor Xa by cleavage of the activation peptide. This reaction is catalyzed by factor VIIa-tissue factor (extrinsic Xase complex) and factor IXa-factor VIIIa (intrinsic Xase complex).[1]
Factor Xa, along with factor Va, calcium, and a phospholipid membrane surface form the prothrombinase complex, to cleave prothrombin to its active form, thrombin.[1]
Structure
Catalytic Triad
Substrate Recognition Sites
The S1 pocket determines binding selectivity for factor Xa. It is formed by loops in residues 214-220 and 189-195 that are linked by a Cys220-Cys191 disulfide bond. Residues 225-228 form the lower portion of the pocket.
The S2 site of factor Xa is formed by the 90s loop which is positioned adjacent to His57. Consistent with glycine as the P2 element in prothrombin, S2 is a small, shallow pocket.
Activation domain
Enzyme Mechanism
General Serine Protease Mechanism
During the acylation half of the reaction Ser195 attacks the carbonyl of the peptide substrate, His57 assists by acting as a general base to yield a tetrahedral intermediate. Asp102 stabilizes the His57-H+ through hydrogen bonding. The tetrahedral intermediate oxyanion is stabilized by interacting with amine groups of the peptide backbone. Upon collapse of the tetrahedral the amine leaving group is expelled with the asstance of His57-H+ acting as a general acid to yield the acylenzyme intermediate. The deacylation portion repeats the same sequence. Water is assisted by His57 to attack the acyl enzyme, to yield another tetrahedral intermediate. Upon intermediate collapse Ser195 and the carboxylic acid product are expelled. [2]
Related Enzymes
References
- ↑ 1.0 1.1 Greer, John (2008). Wintrobe's Clinical Hematology, p. 545-546. Lippincott Williams & Wilkins. ISBN 0781765072.
- ↑ Hedstrom L. Serine protease mechanism and specificity. Chem Rev. 2002 Dec;102(12):4501-24. PMID:12475199
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Jacqueline Gertz, Michal Harel, Alexander Berchansky, David Canner, Jaime Prilusky
