PDBsum entry 3itq

Oxidoreductase

PDB id: 3itq

Contents

Protein chains

198 a.a. *

Ligands

GOL ×2

PO4 ×2

Waters ×193

* Residue conservation analysis

PDB id:

3itq

Name:

Oxidoreductase

Title:

Crystal structure of a prolyl 4-hydroxylase from bacillus anthracis

Structure:

Prolyl 4-hydroxylase, alpha subunit domain protein. Chain: a, b. Engineered: yes

Source:

Bacillus anthracis str.. Anthrax,anthrax bacterium. Organism_taxid: 198094. Strain: ames. Gene: ba_4459, gbaa4459, gbaa_4459, p4h. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.40Å R-factor: 0.196 R-free: 0.211

Authors:

M.A.Culpepper,E.E.Scott,J.Limburg

Key ref:

M.A.Culpepper et al. (2010). Crystal structure of prolyl 4-hydroxylase from Bacillus anthracis. Biochemistry, 49, 124-133. PubMed id: 19947658

Date:

28-Aug-09 Release date: 15-Dec-09

Protein chains

A0A4Y1WAP5  (A0A4Y1WAP5_BACAN) -  Prolyl 4-hydroxylase, alpha subunit domain protein from Bacillus anthracis

Seq: 216 a.a.

Struc: 198 a.a.

Biochemistry 49:124-133 (2010)

PubMed id: 19947658

Crystal structure of prolyl 4-hydroxylase from Bacillus anthracis.

M.A.Culpepper, E.E.Scott, J.Limburg.

ABSTRACT

Prolyl 4-hydroxylases (P4H) catalyze the post-translational hydroxylation of proline residues and play a role in collagen production, hypoxia response, and cell wall development. P4Hs belong to the group of Fe(II)/alphaKG oxygenases and require Fe(II), alpha-ketoglutarate (alphaKG), and O(2) for activity. We report the 1.40 A structure of a P4H from Bacillus anthracis, the causative agent of anthrax, whose immunodominant exosporium protein BclA contains collagen-like repeat sequences. The structure reveals the double-stranded beta-helix core fold characteristic of Fe(II)/alphaKG oxygenases. This fold positions Fe-binding and alphaKG-binding residues in what is expected to be catalytically competent orientations and is consistent with proline peptide substrate binding at the active site mouth. Comparisons of the anthrax P4H structure with Cr P4H-1 structures reveal similarities in a peptide surface groove. However, sequence and structural comparisons suggest differences in conformation of adjacent loops may change the interaction with peptide substrates. These differences may be the basis of a substantial disparity between the K(M) values for the Cr P4H-1 compared to the anthrax and human P4H enzymes. Additionally, while previous structures of P4H enzymes are monomers, B. anthracis P4H forms an alpha(2) homodimer and suggests residues important for interactions between the alpha(2) subunits of alpha(2)beta(2) human collagen P4H. Thus, the anthrax P4H structure provides insight into the structure and function of the alpha-subunit of human P4H, which may aid in the development of selective inhibitors of the human P4H enzyme involved in fibrotic disease.