期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 22, 页码 -出版社
MDPI
DOI: 10.3390/ijms232213966
关键词
lysyl oxidase-like 2; lysine tyrosylquinone; UV-vis spectroscopy; resonance Raman spectroscopy; model chemistry
资金
- National Institutes of Health [R01GM113101]
- Kansas Masonic Cancer Research Institute Pilot Research Program of the University of Kansas Cancer Center [P30CA168524]
- COBRE-PSF [P30 GM110761]
- University of Kansas, Department Chemistry
- National Institutes of Health NIGMS Biotechnology Predoctoral Training Program [T32-GM008359]
- J.K. Lee Summer Scholar Program
- Chaffee Fellowship
- Dains Memorial Scholarship from the Department of Chemistry, the University of Kansas
- National Institutes of Health Training Grant in the Dynamic Aspects of Chemical Biology [T32-GM008545]
This study investigates the spatial arrangement of LTQ and the active site Cu2+ in mature LOXL2. The results suggest that LTQ resides within 2.9 angstrom of the active site of Cu2+, and both LTQ and Cu2+ are solvent-exposed.
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 angstrom Zn2+-bound precursor structure lacking LTQ (PDB:5ZE3) has become available, where Lys653 and Tyr689 are 16.6 angstrom 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 Cu-2. We propose that LTQ resides within 2.9 angstrom of the active site of Cu2+ in the mature LOXL2, and both LTQ and Cu2+ are solvent-exposed.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据