PDBsum entry 2f83

Hydrolase

PDB id: 2f83

Contents

Protein chain

583 a.a. *

Ligands

NAG-NAG

NAG ×2

Metals

_PT ×2

Waters ×53

* Residue conservation analysis

PDB id:

2f83

Name:

Hydrolase

Title:

Crystal structure at 2.9 angstroms resolution of human plasma coagulation factor xi zymogen

Structure:

Coagulation factor xi. Chain: a. Synonym: plasma thromboplastin antecedent, pta, fxi. Ec: 3.4.21.27

Source:

Homo sapiens. Human. Organism_taxid: 9606

Resolution:

2.87Å R-factor: 0.235 R-free: 0.281

Authors:

E.Papagrigoriou,P.A.Mcewan,P.N.Walsh,J.Emsley

Key ref:

E.Papagrigoriou et al. (2006). Crystal structure of the factor XI zymogen reveals a pathway for transactivation. Nat Struct Mol Biol, 13, 557-558. PubMed id: 16699514 DOI: 10.1038/nsmb1095

Date:

01-Dec-05 Release date: 16-May-06

Protein chain

P03951  (FA11_HUMAN) -  Coagulation factor XI from Homo sapiens

Seq: 625 a.a.

Struc: 583 a.a.

DOI no: 10.1038/nsmb1095

Nat Struct Mol Biol 13:557-558 (2006)

PubMed id: 16699514

Crystal structure of the factor XI zymogen reveals a pathway for transactivation.

E.Papagrigoriou, P.A.McEwan, P.N.Walsh, J.Emsley.

ABSTRACT

Factor XI (FXI), a coagulation protein essential to normal hemostasis, circulates as a disulfide-linked dimer. Here we report the full-length FXI zymogen crystal structure, revealing that the protease and four apple domains assemble into a unique 'cup and saucer' architecture. The structure shows that the thrombin and platelet glycoprotein Ib binding sites are remote within the monomer but lie in close proximity across the dimer, suggesting a transactivation mechanism.

Selected figure(s)

Figure 1.
Figure 1. FXI structure. (a) Topology of the four apple domains is represented with the protease domain removed. Connecting loops are colored black and the loop after A4, which leads to the C-terminal protease domain, is colored dark blue. (b) Topology of the FXI dimer with the protease domain colored red and Cys321 disulfide located centrally. (c) Two close-up views of the A4 dimer interface related by a 90° rotation. Left, interacting side chains from one side of the dimer interface are colored yellow, making contact with a charge-surface representation of the other half of the interface (blue, positive; red, negative). Right, a ribbon diagram shows a rotated view of the A4 dimer with hydrogen bonds and electrostatic interactions colored orange.

Figure 2.
Figure 2. FXI activation. (a) Ribbon diagrams representing zymogen activation by superposition of the FXIa structure (green; PDB entry 1ZJD) and the zymogen protease domain (yellow). The region of largest conformation change is the activation loop comprising residues 376–370. Ile370 side chain is colored purple in both structures. Active site Ser557 side chain is also shown. (b) Space-filling representation of the FXI dimer. White side chains, Arg369 and Ile370 from the activation loop; blue side chain, Lys252 and Lys253; red side chain, Glu66.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Mol Biol (2006, 13, 557-558) copyright 2006.