A molecular basis for NO selectivity in soluble guanylate cyclase

被引：155

作者：

Boon, EM

Huang, SH

Marletta, MA ^{[1
]}

机构：

[1] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA

[2] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA

[3] Lawrence Berkeley Natl Lab, Div Phys Biosci, Berkeley, CA 94720 USA

来源：

NATURE CHEMICAL BIOLOGY | 2005年 / 1卷 / 01期

关键词：

D O I：

10.1038/nchembio704

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Soluble guanylate cyclases (sGCs) function as heme sensors that selectively bind nitric oxide (NO), triggering reactions essential to animal physiology. Recent discoveries place sGCs in the H-NOX family (heme nitric oxide/oxygen-binding domain), which includes bacterial proteins from aerobic and anaerobic organisms. Some H-NOX proteins tightly bind oxygen (O-2), whereas others show no measurable affinity for O-2, providing the basis for selective NO signaling in aerobic cells. Using a series of wild-type and mutant H-NOXs, we established a molecular basis for ligand discrimination. A distal pocket tyrosine is requisite for O-2 binding in the H-NOX family. These data suggest that sGC uses a kinetic selection against O-2; we propose that the O-2 dissociation rate in the absence of this tyrosine is fast and that a stable O-2 complex does not form.

引用

页码：53 / 59

页数：7

共 31 条

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