PDBsum entry 6evm

Hydrolase

PDB id: 6evm

Contents

Protein chain

95 a.a.

Ligands

PRO-PRO-PRO-PRO-PRO-PRO-PRO-PRO-PRO

SO4

DMS

Waters ×106

PDB id:

6evm

Name:

Hydrolase

Title:

Crystal structure of a pro-9 complexed peptide-substrate-binding domain of human type ii collagen prolyl 4-hydroxylase

Structure:

Prolyl 4-hydroxylase subunit alpha-2. Chain: a. Synonym: 4-ph alpha-2,procollagen-proline,2-oxoglutarate-4- dioxygenase subunit alpha-2. Engineered: yes. Pro-9. Chain: c. Engineered: yes. Other_details: synthetic peptide having 9 proline residues.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: p4ha2, unq290/pro330. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Synthetic construct. Organism_taxid: 32630

Resolution:

2.00Å R-factor: 0.175 R-free: 0.219

Authors:

A.V.Murthy,R.Sulu,M.K.Koski,R.K.Wierenga

Key ref:

A.V.Murthy et al. (2018). Structural enzymology binding studies of the peptide-substrate-binding domain of human collagen prolyl 4-hydroxylase (type-II): High affinity peptides have a PxGP sequence motif. Protein Sci, 27, 1692-1703. PubMed id: 30168208

Date:

02-Nov-17 Release date: 12-Sep-18

Protein chain

O15460  (P4HA2_HUMAN) -  Prolyl 4-hydroxylase subunit alpha-2 from Homo sapiens

Seq: 535 a.a.

Struc: 95 a.a.

Enzyme reactions

• Enzyme class: E.C.1.14.11.2 - procollagen-proline 4-dioxygenase.
• Reaction: L-prolyl-[collagen] + 2-oxoglutarate + O2 = trans-4-hydroxy-L-prolyl- [collagen] + succinate + CO2

L-prolyl-[collagen] (Bound ligand (Het Group name = PRO) matches with 63.64% similarity) + 2-oxoglutarate + O2 = trans-4-hydroxy-L-prolyl- [collagen] + succinate + CO2

• Cofactor: Fe(2+); L-ascorbate

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

reference

Protein Sci 27:1692-1703 (2018)

PubMed id: 30168208

Structural enzymology binding studies of the peptide-substrate-binding domain of human collagen prolyl 4-hydroxylase (type-II): High affinity peptides have a PxGP sequence motif.

A.V.Murthy, R.Sulu, M.K.Koski, H.Tu, J.Anantharajan, S.K.Sah-Teli, J.Myllyharju, R.K.Wierenga.

ABSTRACT

The peptide-substrate-binding (PSB) domain of collagen prolyl 4-hydroxylase (C-P4H, an α₂ β₂ tetramer) binds proline-rich procollagen peptides. This helical domain (the middle domain of the α subunit) has an important role concerning the substrate binding properties of C-P4H, although it is not known how the PSB domain influences the hydroxylation properties of the catalytic domain (the C-terminal domain of the α subunit). The crystal structures of the PSB domain of the human C-P4H isoform II (PSB-II) complexed with and without various short proline-rich peptides are described. The comparison with the previously determined PSB-I peptide complex structures shows that the C-P4H-I substrate peptide (PPG)₃ , has at most very weak affinity for PSB-II, although it binds with high affinity to PSB-I. The replacement of the middle PPG triplet of (PPG)₃ to the nonhydroxylatable PAG, PRG, or PEG triplet, increases greatly the affinity of PSB-II for these peptides, leading to a deeper mode of binding, as compared to the previously determined PSB-I peptide complexes. In these PSB-II complexes, the two peptidyl prolines of its central P(A/R/E)GP region bind in the Pro5 and Pro8 binding pockets of the PSB peptide-binding groove, and direct hydrogen bonds are formed between the peptide and the side chains of the highly conserved residues Tyr158, Arg223, and Asn227, replacing water mediated interactions in the corresponding PSB-I complex. These results suggest that PxGP (where x is not a proline) is the common motif of proline-rich peptide sequences that bind with high affinity to PSB-II.