6ax7: Difference between revisions
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==The crystal structure of a lysyl hydroxylase from Acanthamoeba polyphaga mimivirus== | ==The crystal structure of a lysyl hydroxylase from Acanthamoeba polyphaga mimivirus== | ||
<StructureSection load='6ax7' size='340' side='right' caption='[[6ax7]], [[Resolution|resolution]] 2.00Å' scene=''> | <StructureSection load='6ax7' size='340' side='right'caption='[[6ax7]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6ax7]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AX7 OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[6ax7]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Acanthamoeba_polyphaga_mimivirus Acanthamoeba polyphaga mimivirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AX7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AX7 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.002Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6ax7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ax7 OCA], [https://pdbe.org/6ax7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ax7 RCSB], [https://www.ebi.ac.uk/pdbsum/6ax7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ax7 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/PLOD_MIMIV PLOD_MIMIV] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Acanthamoeba polyphaga mimivirus]] | ||
[[Category: Alvarado | [[Category: Large Structures]] | ||
[[Category: Guo | [[Category: Alvarado S]] | ||
[[Category: Kurie | [[Category: Guo H]] | ||
[[Category: Miller | [[Category: Kurie JM]] | ||
[[Category: Phillips | [[Category: Miller MD]] | ||
[[Category: Tainer | [[Category: Phillips Jr GN]] | ||
[[Category: Tsai | [[Category: Tainer JA]] | ||
[[Category: Tsai C]] | |||
Latest revision as of 17:27, 4 October 2023
The crystal structure of a lysyl hydroxylase from Acanthamoeba polyphaga mimivirusThe crystal structure of a lysyl hydroxylase from Acanthamoeba polyphaga mimivirus
Structural highlights
FunctionPublication Abstract from PubMedCollagen lysyl hydroxylases (LH1-3) are Fe(2+)- and 2-oxoglutarate (2-OG)-dependent oxygenases that maintain extracellular matrix homeostasis. High LH2 levels cause stable collagen cross-link accumulations that promote fibrosis and cancer progression. However, developing LH antagonists will require structural insights. Here, we report a 2 A crystal structure and X-ray scattering on dimer assemblies for the LH domain of L230 in Acanthamoeba polyphaga mimivirus. Loop residues in the double-stranded beta-helix core generate a tail-to-tail dimer. A stabilizing hydrophobic leucine locks into an aromatic tyrosine-pocket on the opposite subunit. An active site triad coordinates Fe(2+). The two active sites flank a deep surface cleft that suggest dimerization creates a collagen-binding site. Loss of Fe(2+)-binding disrupts the dimer. Dimer disruption and charge reversal in the cleft increase Km and reduce LH activity. Ectopic L230 expression in tumors promotes collagen cross-linking and metastasis. These insights suggest inhibitor targets for fibrosis and cancer. Pro-metastatic collagen lysyl hydroxylase dimer assemblies stabilized by Fe(2+)-binding.,Guo HF, Tsai CL, Terajima M, Tan X, Banerjee P, Miller MD, Liu X, Yu J, Byemerwa J, Alvarado S, Kaoud TS, Dalby KN, Bota-Rabassedas N, Chen Y, Yamauchi M, Tainer JA, Phillips GN Jr., Kurie JM Nat Commun. 2018 Feb 6;9(1):512. doi: 10.1038/s41467-018-02859-z. PMID:29410444[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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