6ax7: Difference between revisions
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The | ==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=''> | |||
== Structural highlights == | |||
<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='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='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'>[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> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PLOD_MIMIV PLOD_MIMIV] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Collagen 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<ref>PMID:29410444</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6ax7" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Acanthamoeba polyphaga mimivirus]] | |||
[[Category: Large Structures]] | |||
[[Category: Alvarado S]] | |||
[[Category: Guo H]] | |||
[[Category: Kurie JM]] | |||
[[Category: Miller MD]] | |||
[[Category: Phillips Jr GN]] | |||
[[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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