View source for 9hre


==Peptide-substrate-binding (PSB) domain of human type I collagen prolyl 4-hydroxylase complexed with Pro-Hyp-Gly-Pro-Ala-Gly-Pro-Hyp-Gly.==
<StructureSection load='9hre' size='340' side='right'caption='[[9hre]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9hre]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9HRE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9HRE FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.05&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLY:GLYCINE'>GLY</scene>, <scene name='pdbligand=HYP:4-HYDROXYPROLINE'>HYP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=MPO:3[N-MORPHOLINO]PROPANE+SULFONIC+ACID'>MPO</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9hre FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9hre OCA], [https://pdbe.org/9hre PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9hre RCSB], [https://www.ebi.ac.uk/pdbsum/9hre PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9hre ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/P4HA1_HUMAN P4HA1_HUMAN] Catalyzes the post-translational formation of 4-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Collagen prolyl 4-hydroxylase (C-P4H) catalyzes the 4-hydroxylation of Y-prolines of the XYG-repeat of procollagen. C-P4Hs are tetrameric alpha(2)beta(2) enzymes. The alpha-subunit provides the N-terminal dimerization domain, the middle peptide-substrate-binding (PSB) domain, and the C-terminal catalytic (CAT) domain. There are three isoforms of the alpha-subunit, complexed with a beta-subunit that is protein disulfide isomerase, forming C-P4H I-III. The PSB domain of the alpha-subunit binds proline-rich peptides, but its function with respect to the prolyl hydroxylation mechanism is unknown. An extended mode of binding of proline-rich peptides (PPII, polyproline type-II, conformation) to the PSB-I domain has previously been reported for the PPG-PPG-PPG and P9 peptides. Crystal structures now show that peptides with the motif PxGP (PPG-PRG-PPG, PPG-PAG-PPG) (where x, at Y-position 5, is not a proline) bind to the PSB-I domain differently, more deeply, in the peptide-binding groove. The latter mode of binding has previously been reported for structures of the PSB-II domain complexed with these PxGP-peptides. In addition, it is shown here by crystallographic binding studies that the POG-PAG-POG peptide (with 4-hydroxyprolines at Y-positions 2 and 8) also adopts the PxGP mode of binding to PSB-I as well as to PSB-II. Calorimetric binding studies show that the affinities of these peptides are lower for PSB-I than for PSB-II, with, respectively, K(D) values of about 70 muM for PSB-I and 20 muM for PSB-II. The importance of these results for understanding the reaction mechanism of C-P4H, in particular concerning the function of the PSB domain, is discussed.

Binding Differences of the Peptide-Substrate-Binding Domain of Collagen Prolyl 4-Hydroxylases I and II for Proline- and Hydroxyproline-Rich Peptides.,Rahman MM, Sulu R, Adediran B, Tu H, Salo AM, Murthy S, Myllyharju J, Wierenga RK, Koski MK Proteins. 2025 Oct;93(10):1732-1746. doi: 10.1002/prot.26839. Epub 2025 May 19. PMID:40386874<ref>PMID:40386874</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9hre" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Koski MK]]
[[Category: Rahman MM]]
[[Category: Sulu R]]
[[Category: Wierenga RK]]