期刊
ANTIOXIDANTS & REDOX SIGNALING
卷 17, 期 9, 页码 1246-1263出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/ars.2012.4564
关键词
-
资金
- U.S. Public Health Service [HL088128, HL095820, GM35649, HL47020]
- American Heart Association, South Central Affiliate [09GRNT2060182]
- Robert A. Welch Foundation [C0612]
Significance: Ligand selectivity for dioxygen (O-2), carbon monoxide (CO), and nitric oxide (NO) is critical for signal transduction and is tailored specifically for each heme-protein sensor. Key NO sensors, such as soluble guanylyl cyclase (sGC), specifically recognized low levels of NO and achieve a total O-2 exclusion. Several mechanisms have been proposed to explain the O-2 insensitivity, including lack of a hydrogen bond donor and negative electrostatic fields to selectively destabilize bound O-2, distal steric hindrance of all bound ligands to the heme iron, and restriction of in-plane movements of the iron atom. Recent Advances: Crystallographic structures of the gas sensors, Thermoanaerobacter tengcongensis heme-nitric oxide/oxygen-binding domain (Tt H-NOX1) or Nostoc puntiforme (Ns) H-NOX, and measurements of O-2 binding to site-specific mutants of Tt H-NOX and the truncated beta subunit of sGC suggest the need for a H-bonding donor to facilitate O-2 binding. Critical Issues: However, the O-2 insensitivity of full length sGC with a site-specific replacement of isoleucine by a tyrosine on residue 145 and the very slow autooxidation of Ns H-NOX and cytochrome c' suggest that more complex mechanisms have evolved to exclude O-2 but retain high affinity NO binding. A combined graphical analysis of ligand binding data for libraries of heme sensors, globins, and model heme shows that the NO sensors dramatically inhibit the formation of six-coordinated NO, CO, and O-2 complexes by direct distal steric hindrance (cyt c'), proximal constraints of in-plane iron movement (sGC), or combinations of both following a sliding scale rule. High affinity NO binding in H-NOX proteins is achieved by multiple NO binding steps that produce a high affinity five-coordinate NO complex, a mechanism that also prevents NO dioxygenation. Future Directions: Knowledge advanced by further extensive test of this sliding scale rule hypothesis should be valuable in guiding novel designs for heme based sensors. Antioxid. Redox Signal. 17, 1246-1263.
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