PDBsum entry 5eod

Hydrolase

PDB id: 5eod

Contents

Protein chain

586 a.a.

Ligands

GLU-PHE-PRO-ASP-PHE-PRO

NAG ×3

PDB id:

5eod

Name:

Hydrolase

Title:

Human plasma coagulation fxi with peptide lp2

Structure:

Coagulation factor xi. Chain: a. Synonym: fxi,plasma thromboplastin antecedent,pta. Engineered: yes. Lp2. Chain: b. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: f11. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Expressed in: synthetic construct. Expression_system_taxid: 32630

Resolution:

3.10Å R-factor: 0.194 R-free: 0.274

Authors:

S.S.Wong,S.Ostergaard,G.Hall,C.Li,P.M.Williams,H.Stennicke,J.Emsley

Key ref:

S.S.Wong et al. (2016). A novel DFP tripeptide motif interacts with the coagulation factor XI apple 2 domain. Blood, 127, 2915-2923. PubMed id: 27006387 DOI: 10.1182/blood-2015-10-676122

Date:

10-Nov-15 Release date: 06-Apr-16

Protein chain

P03951  (FA11_HUMAN) -  Coagulation factor XI from Homo sapiens

Seq: 625 a.a.

Struc: 586 a.a.

Enzyme reactions

• Enzyme class: E.C.3.4.21.27 - coagulation factor XIa.
• Reaction: Selective cleavage of Arg-|-Ala and Arg-|-Val bonds in factor IX to form factor IXa.

DOI no: 10.1182/blood-2015-10-676122

Blood 127:2915-2923 (2016)

PubMed id: 27006387

A novel DFP tripeptide motif interacts with the coagulation factor XI apple 2 domain.

S.S.Wong, S.Østergaard, G.Hall, C.Li, P.M.Williams, H.Stennicke, J.Emsley.

ABSTRACT

Factor XI (FXI) is the zymogen of FXIa, which cleaves FIX in the intrinsic pathway of coagulation. FXI is known to exist as a dimer and interacts with multiple proteins via its 4 apple domains in the "saucer section" of the enzyme; however, to date, no complex crystal structure has been described. To investigate protein interactions of FXI, a large random peptide library consisting of 10(6) to 10(7) peptides was screened for FXI binding, which identified a series of FXI binding motifs containing the signature Asp-Phe-Pro (DFP) tripeptide. Motifs containing this core tripeptide were found in diverse proteins, including the known ligand high-molecular-weight kininogen (HK), as well as the extracellular matrix proteins laminin and collagen V. To define the binding site on FXI, we determined the crystal structure of FXI in complex with the HK-derived peptide NPISDFPDT. This revealed the location of the DFP peptide bound to the FXI apple 2 domain, and central to the interaction, the DFP phenylalanine side-chain inserts into a major hydrophobic pocket in the apple 2 domain and the isoleucine occupies a flanking minor pocket. Two further structures of FXI in complex with the laminin-derived peptide EFPDFP and a DFP peptide from the random screen demonstrated binding in the same pocket, although in a slightly different conformation, thus revealing some flexibility in the molecular interactions of the FXI apple 2 domain.