PDBsum entry 1e5s

Oxygenase

PDB id: 1e5s

Contents

Protein chains

260 a.a. *

243 a.a. *

Ligands

SO4

Metals

FE2 ×2

Waters ×216

* Residue conservation analysis

PDB id:

1e5s

Name:

Oxygenase

Title:

Proline 3-hydroxylase (type ii) - iron form

Structure:

Proline oxidase. Chain: a, b

Source:

Streptomyces sp.. Organism_taxid: 60871. Strain: th1

Biol. unit:

Homo-Dimer (from PDB file)

Resolution:

2.40Å R-factor: 0.216 R-free: 0.271

Authors:

I.J.Clifton,L.C.Hsueh,J.E.Baldwin,C.J.Schofield,K.Harlos

Key ref:

I.J.Clifton et al. (2001). Structure of proline 3-hydroxylase. Evolution of the family of 2-oxoglutarate dependent oxygenases. Eur J Biochem, 268, 6625-6636. PubMed id: 11737217 DOI: 10.1046/j.0014-2956.2001.02617.x

Date:

28-Jul-00 Release date: 26-Jul-01

Protein chain

O09345  (P3H2_STRSQ) -  L-proline cis-3-hydroxylase 2 from Streptomyces sp

Seq: 290 a.a.

Struc: 260 a.a.

Protein chain

O09345  (P3H2_STRSQ) -  L-proline cis-3-hydroxylase 2 from Streptomyces sp

Seq: 290 a.a.

Struc: 243 a.a.

Enzyme reactions

• Enzyme class: Chains A, B: E.C.1.14.11.28 - proline 3-hydroxylase.
• Reaction: L-proline + 2-oxoglutarate + O2 = cis-3-hydroxy-L-proline + succinate + CO2
• Cofactor: Fe(2+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1046/j.0014-2956.2001.02617.x

Eur J Biochem 268:6625-6636 (2001)

PubMed id: 11737217

Structure of proline 3-hydroxylase. Evolution of the family of 2-oxoglutarate dependent oxygenases.

I.J.Clifton, L.C.Hsueh, J.E.Baldwin, K.Harlos, C.J.Schofield.

ABSTRACT

Iron (II)/2-oxoglutarate (2-OG)-dependent oxygenases catalyse oxidative reactions in a range of metabolic processes including the hydroxylation of proline and lysine residues during the post-translational modification of collagen. 2-OG oxygenases commonly require ascorbate for full activity. In the vitamin C deficient disease, scurvy, reduced activity of 2-OG oxygenases results in impaired formation of collagen. Here we report the crystal structure of bacterial proline 3-hydroxylase from Streptomyces sp., an enzyme which hydroxylates proline at position 3, the first of a 2-OG oxygenase catalysing oxidation of a free alpha-amino acid. Structures were obtained for the enzyme in the absence of iron (to 2.3A resolution, R=20.2%, Rfree=25.3%) and that complexed to iron (II) (to 2.4A resolution, R=19.8%, Rfree=22.6%). The structure contains conserved motifs present in other 2-OG oxygenases including a 'jelly roll' beta strand core and residues binding iron and 2-oxoglutarate, consistent with divergent evolution within the extended family. The structure differs significantly from many other 2-OG oxygenases in possessing a discrete C-terminal helical domain. Analysis of the structure suggests a model for proline binding and a mechanism for uncoupling of proline and 2-OG turnover.

Selected figure(s)

Figure 1.
Fig. 1 Reaction summary. Reactions catalysed by mononuclear nonhaem iron oxygenases (A) proline 3-hydroxylase (P-3-H) (B) proline-4-hydroxylase (C) one of the reactions catalysed by deacetoxycephalosporin C synthase (DAOCS) (D) isopenicillin N synthase (IPNS) (E) clavaminic acid synthase (CAS) (F) p-hydroxyphenylpyruvate dioxygenase (HPPD).

Figure 4.
Fig. 4 View of the P-3-H active site. The active site of the enzyme (molecule A) cocrystallized with iron(II) sulfate. The -barrel core is in green, the iron binding ligands in purple, the iron in orange and the N-terminal region and C-terminal domain in magenta. The ferrous iron is ligated by the side chains of His107, Asp109 and His158. Note: (a) Arg168, Ser170 and His135 which are probably involved in binding 2-OG; (b) Arg95, Arg97, Arg122 and His43 which may bind the proline carboxylate; (c) the disordered loop (in orange) containing six sequential acidic residues, which may bind the imino group of proline.

The above figures are reprinted by permission from the Federation of European Biochemical Societies: Eur J Biochem (2001, 268, 6625-6636) copyright 2001.

Figures were selected by an automated process.