PDBsum entry 2aiq

Hydrolase

PDB id: 2aiq

Contents

Protein chain

231 a.a. *

Ligands

NAG ×3

SO4

ACT

BEN

GOL

Metals

_CL

Waters ×229

* Residue conservation analysis

PDB id:

2aiq

Name:

Hydrolase

Title:

Crystal structure of benzamidine-inhibited protein c activator from the venom of copperhead snake agkistrodon contortrix contortrix

Structure:

Protein c activator. Chain: a. Synonym: venombin a, ancrod, acc-c. Ec: 3.4.21.74

Source:

Agkistrodon contortrix contortrix. Southern copperhead. Organism_taxid: 8713. Strain: contortrix

Resolution:

1.54Å R-factor: 0.169 R-free: 0.191

Authors:

M.T.Murakami,R.K.Arni

Key ref:

M.T.Murakami and R.K.Arni (2005). Thrombomodulin-independent activation of protein C and specificity of hemostatically active snake venom serine proteinases: crystal structures of native and inhibited Agkistrodon contortrix contortrix protein C activator. J Biol Chem, 280, 39309-39315. PubMed id: 16162508 DOI: 10.1074/jbc.M508502200

Date:

30-Jul-05 Release date: 06-Sep-05

Protein chain

P09872  (VSPCA_AGKCO) -  Protein C activator from Agkistrodon contortrix contortrix

Seq: 231 a.a.

Struc: 231 a.a.

Enzyme reactions

• Enzyme class: E.C.3.4.21.- - ?????

DOI no: 10.1074/jbc.M508502200

J Biol Chem 280:39309-39315 (2005)

PubMed id: 16162508

Thrombomodulin-independent activation of protein C and specificity of hemostatically active snake venom serine proteinases: crystal structures of native and inhibited Agkistrodon contortrix contortrix protein C activator.

M.T.Murakami, R.K.Arni.

ABSTRACT

Protein C activation initiated by the thrombin-thrombomodulin complex forms the major physiological anticoagulant pathway. Agkistrodon contortrix contortrix protein C activator, a glycosylated single-chain serine proteinase, activates protein C without relying on thrombomodulin. The crystal structures of native and inhibited Agkistrodon contortrix contortrix protein C activator determined at 1.65 and 1.54 A resolutions, respectively, indicate the pivotal roles played by the positively charged belt and the strategic positioning of the three carbohydrate moieties surrounding the catalytic site in protein C recognition, binding, and activation. Structural changes in the benzamidine-inhibited enzyme suggest a probable function in allosteric regulation for the anion-binding site located in the C-terminal extension, which is fully conserved in snake venom serine proteinases, that preferentially binds Cl(1-) instead of SO(4)(2-).

Selected figure(s)

Figure 2.
FIGURE 2. Electron densities and interactions observed for the benzamidine molecule (A) and the sulfate ion at the S1 subsite and the catalytic site (B), respectively. The electron densities (blue cages) are contoured at the 1 level in the 2F[o] - F[c] map; interrupted lines and numbers indicate hydrogen bonds and distances, respectively.

Figure 6.
FIGURE 6. Surface charge distribution of the channel leading to the catalytic site in ACC-C (A) and TSV-PA (B) in the same relative orientation. The S1 subsites are indicated by yellow arrows. C, surface charge of protein C zymogen; the yellow ring indicates the position of the modeled activation peptide. D, stereo view of the proposed interactions of the modeled activation peptide of protein C (stick model) in the active site cleft (charged surface).

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2005, 280, 39309-39315) copyright 2005.

Figures were selected by an automated process.