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Insight into the Spatial Arrangement of the Lysine Tyrosylquinone and Cu2+ in the Active Site of Lysyl Oxidase-like 2
dc.contributor.author | Meier, Alex A. | |
dc.contributor.author | Moon, Hee-Jung | |
dc.contributor.author | Sabuncu, Sinan | |
dc.contributor.author | Singh, Priya | |
dc.contributor.author | Ronnebaum, Trey A. | |
dc.contributor.author | Ou, Siyu | |
dc.contributor.author | Douglas, Justin T. | |
dc.contributor.author | Jackson, Timothy A. | |
dc.contributor.author | Moënne-Loccoz, Pierre | |
dc.contributor.author | Mure, Minae | |
dc.date.accessioned | 2023-02-09T20:09:15Z | |
dc.date.available | 2023-02-09T20:09:15Z | |
dc.date.issued | 2022-11-12 | |
dc.identifier.citation | Meier, A.A.; Moon, H.-J.; Sabuncu, S.; Singh, P.; Ronnebaum, T.A.; Ou, S.; Douglas, J.T.; Jackson, T.A.; Moënne-Loccoz, P.; Mure, M. Insight into the Spatial Arrangement of the Lysine Tyrosylquinone and Cu2+ in the Active Site of Lysyl Oxidase-like 2. Int. J. Mol. Sci. 2022, 23, 13966. https://doi.org/10.3390/ijms232213966 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/33766 | |
dc.description.abstract | Lysyl oxidase-2 (LOXL2) is a Cu2+ and lysine tyrosylquinone (LTQ)-dependent amine oxidase that catalyzes the oxidative deamination of peptidyl lysine and hydroxylysine residues to promote crosslinking of extracellular matrix proteins. LTQ is post-translationally derived from Lys653 and Tyr689, but its biogenesis mechanism remains still elusive. A 2.4 Å Zn2+-bound precursor structure lacking LTQ (PDB:5ZE3) has become available, where Lys653 and Tyr689 are 16.6 Å apart, thus a substantial conformational rearrangement is expected to take place for LTQ biogenesis. However, we have recently shown that the overall structures of the precursor (no LTQ) and the mature (LTQ-containing) LOXL2s are very similar and disulfide bonds are conserved. In this study, we aim to gain insights into the spatial arrangement of LTQ and the active site Cu2+ in the mature LOXL2 using a recombinant LOXL2 that is inhibited by 2-hydrazinopyridine (2HP). Comparative UV-vis and resonance Raman spectroscopic studies of the 2HP-inhibited LOXL2 and the corresponding model compounds and an EPR study of the latter support that 2HP-modified LTQ serves as a tridentate ligand to the active site Cu2. We propose that LTQ resides within 2.9 Å of the active site of Cu2+ in the mature LOXL2, and both LTQ and Cu2+ are solvent-exposed. | en_US |
dc.publisher | MDPI | en_US |
dc.rights | © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.subject | Lysyl oxidase-like 2 | en_US |
dc.subject | Lysine tyrosylquinone | en_US |
dc.subject | UV-vis spectroscopy | en_US |
dc.subject | Resonance Raman spectroscopy | en_US |
dc.subject | Model chemistry | en_US |
dc.title | Insight into the Spatial Arrangement of the Lysine Tyrosylquinone and Cu2+ in the Active Site of Lysyl Oxidase-like 2 | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Meier, Alex A. | |
kusw.kuauthor | Moon, Hee-Jung | |
kusw.kuauthor | Singh, Priya | |
kusw.kuauthor | Ronnebaum, Trey A. | |
kusw.kuauthor | Ou, Siyu | |
kusw.kuauthor | Douglas, Justin T. | |
kusw.kuauthor | Jackson, Timothy A. | |
kusw.kuauthor | Mure, Minae | |
kusw.kudepartment | Chemistry | en_US |
dc.identifier.doi | 10.3390/ijms232213966 | en_US |
dc.identifier.orcid | https://orcid.org/0000-0001-8346-8175 | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-9214-3564 | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-3529-2715 | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-7684-7617 | en_US |
kusw.oaversion | Scholarly/refereed, publisher version | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC9694262 | en_US |
dc.rights.accessrights | openAccess | en_US |