PDBsum entry 1de7

Hydrolase/hydrolase substrate

PDB id: 1de7

Contents

Protein chains

28 a.a. *

249 a.a. *

26 a.a. *

11 a.a. *

Metals

_NA ×2

Waters ×479

* Residue conservation analysis

PDB id:

1de7

Name:

Hydrolase/hydrolase substrate

Title:

Interaction of factor xiii activation peptide with alpha-thrombin: crystal structure of the enzyme-substrate complex

Structure:

Alpha-thrombin (light chain). Chain: l, j. Alpha-thrombin (heavy chain). Chain: h, k. Factor xiii activation peptide (28-37). Chain: a, b. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Tissue: plasma. Synthetic: yes

Biol. unit:

Trimer (from PQS)

Resolution:

2.00Å R-factor: 0.194 R-free: 0.257

Authors:

C.Sadasivan,V.C.Yee

Key ref:

C.Sadasivan and V.C.Yee (2000). Interaction of the factor XIII activation peptide with alpha -thrombin. Crystal structure of its enzyme-substrate analog complex. J Biol Chem, 275, 36942-36948. PubMed id: 10956659 DOI: 10.1074/jbc.M006076200

Date:

13-Nov-99 Release date: 13-Dec-00

Protein chain

P00734  (THRB_HUMAN) -  Prothrombin from Homo sapiens

Seq: 622 a.a.

Struc: 28 a.a.

Protein chains

P00734  (THRB_HUMAN) -  Prothrombin from Homo sapiens

Seq: 622 a.a.

Struc: 249 a.a.

Protein chain

P00734  (THRB_HUMAN) -  Prothrombin from Homo sapiens

Seq: 622 a.a.

Struc: 26 a.a.

Protein chains

No UniProt id for this chain

Struc: 11 a.a.

Enzyme reactions

• Enzyme class: Chains L, H, J, K: E.C.3.4.21.5 - thrombin.
• Reaction: Preferential cleavage: Arg-|-Gly; activates fibrinogen to fibrin and releases fibrinopeptide A and B.

DOI no: 10.1074/jbc.M006076200

J Biol Chem 275:36942-36948 (2000)

PubMed id: 10956659

Interaction of the factor XIII activation peptide with alpha -thrombin. Crystal structure of its enzyme-substrate analog complex.

C.Sadasivan, V.C.Yee.

ABSTRACT

The serine protease thrombin proteolytically activates blood coagulation factor XIII by cleavage at residue Arg(37); factor XIII in turn cross-links fibrin molecules and gives mechanical stability to the blood clot. The 2.0-A resolution x-ray crystal structure of human alpha-thrombin bound to the factor XIII-(28-37) decapeptide has been determined. This structure reveals the detailed atomic level interactions between the factor XIII activation peptide and thrombin and provides the first high resolution view of this functionally important part of the factor XIII molecule. A comparison of this structure with the crystal structure of fibrinopeptide A complexed with thrombin highlights several important determinants of thrombin substrate interaction. First, the P1 and P2 residues must be compatible with the geometry and chemistry of the S1 and S2 specificity sites in thrombin. Second, a glycine in the P5 position is necessary for the conserved substrate conformation seen in both factor XIII-(28-37) and fibrinopeptide A. Finally, the hydrophobic residues, which occupy the aryl binding site of thrombin determine the substrate conformation further away from the catalytic residues. In the case of factor XIII-(28-37), the aryl binding site is shared by hydrophobic residues P4 (Val(34)) and P9 (Val(29)). A bulkier residue in either of these sites may alter the substrate peptide conformation.

Selected figure(s)

Figure 3.
Fig. 3. Schematic representation of van der Waals interactions ( 4 Å) of thrombin with fXIII -(28-37) PEP1 (top) and FPA (15) (bottom). Interactions with the underlined residues are observed only in the given complex.

Figure 6.
Fig. 6. Superposition of Val34 in fXIII -(28-37) and surrounding thrombin residues. (PEP1, red; PEP2, green; FPA, blue; PPACK, magenta). The presence of the Val34 side chain in fXIII-(28-37) makes a shift in surrounding thrombin residues.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2000, 275, 36942-36948) copyright 2000.

Figures were selected by an automated process.