6EVP

Crystal structure the peptide-substrate-binding domain of human type II collagen prolyl 4-hydroxylase complexed with Pro-Pro-Gly-Pro-Glu-Gly-Pro-Pro-Gly.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.68 Å
  • R-Value Free: 0.215 
  • R-Value Work: 0.183 
  • R-Value Observed: 0.186 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

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.

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

(2018) Protein Sci 27: 1692-1703

  • DOI: https://doi.org/10.1002/pro.3450
  • Primary Citation of Related Structures:  
    6EVL, 6EVM, 6EVN, 6EVO, 6EVP

  • PubMed Abstract: 

    The peptide-substrate-binding (PSB) domain of collagen prolyl 4-hydroxylase (C-P4H, an α 2 β 2 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.


  • Organizational Affiliation

    Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Prolyl 4-hydroxylase subunit alpha-2102Homo sapiensMutation(s): 0 
Gene Names: P4HA2UNQ290/PRO330
EC: 1.14.11.2
UniProt & NIH Common Fund Data Resources
Find proteins for O15460 (Homo sapiens)
Explore O15460 
Go to UniProtKB:  O15460
PHAROS:  O15460
GTEx:  ENSG00000072682 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO15460
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
PRO-PRO-GLY-PRO-GLU-GLY-PRO-PRO-GLYB [auth C]9synthetic constructMutation(s): 0 
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.68 Å
  • R-Value Free: 0.215 
  • R-Value Work: 0.183 
  • R-Value Observed: 0.186 
  • Space Group: P 32 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 55.02α = 90
b = 55.02β = 90
c = 73.269γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
Aimlessdata scaling
PHENIXphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Sigrid Juselius FoundationFinland--

Revision History  (Full details and data files)

  • Version 1.0: 2018-09-12
    Type: Initial release
  • Version 1.1: 2018-10-31
    Changes: Data collection, Database references