Volume 5 Supplement 1
Molecular steps in soluble guanylate cyclase activation
© BioMed Central Ltd 2005
Published: 16 June 2005
Soluble guanylate cyclase (sGC) is a hemoprotein that is selectively activated by specifically binding NO. Once activated sGC synthesizes cyclic GMP from GTP which then triggers reactions essential to animal physiology. sGC essentially functions as a selective sensor for NO. sGC belongs to a recently identified group of proteins termed the H-NOX family (Heme Nitric oxide/OXygen binding proteins) that includes bacterial counterparts from aerobic and anaerobic organisms [1–4]. Based on our recent structure of a family member , a molecular basis for the ligand discrimination against O2 in NO-regulated sGCs has been established. Further studies have pointed towards O2-regulated sGCs in C. elegans . NO binding to the heme remains as a key molecular activation step; however, it has become clear that activation and deactivation are regulated in a complex manner [6, 7]. In the accepted model shown below, NO binds to the sGC heme, activating the enzyme after conversion to the 5-coordinate nitrosyl complex.
We gratefully acknowledge financial support from the Aldo DeBenedictis Fund, LDRD fund from the Lawrence Berkeley National Laboratory and the National Institutes of Health.
- Iyer LM, Anantharaman V, Aravind L: Ancient conserved domains shared by animal soluble guanylyl cyclases and bacterial signaling proteins. BMC Genomics. 2003, 6: 5-10.1186/1471-2164-4-5.View ArticleGoogle Scholar
- Karow DS, Pan D, Pellicena P, Presley A, Mathies RA, Marletta MA: Spectroscopic characterization of the sGC-like heme domains from Vibrio cholerae and Thermoanaerobacter tengcongensis. Biochemistry. 2004, 43: 10203-10211. 10.1021/bi049374l.View ArticlePubMedGoogle Scholar
- Pellicena P, Karow DS, Boon EM, Marletta MA, Kuriyan J: Crystal structure of an oxygen binding H-NOX domain related to soluble guanylate cyclases. Proc Natl Acad Sci U S A. 2004, 101: 12854-12859. 10.1073/pnas.0405188101.PubMed CentralView ArticlePubMedGoogle Scholar
- Boon EM, Huang SH, Marletta MA: A molecular basis for NO selectivity in soluble guanylate cyclase. Nature Chemical Biology. 2005,Google Scholar
- Gray JM, Karow DS, Lu H, Chang AJ, Chang JS, Ellis RE, Marletta MA, Bargmann CI: Oxygen sensation and social feeding mediated by a C. elegans guanylate cyclase homologue. Nature. 2004, 430: 317-322. 10.1038/nature02714.View ArticlePubMedGoogle Scholar
- Cary SPL, Winger JA, Marletta MA: Tonic and acute nitric oxide signaling through soluble guanylate cyclase is mediated by non-heme NO, ATP, and GTP. 2005,Google Scholar
- Russwurm M, Koesling D: NO activation of guanylyl cyclase. Embo J. 2004, 23: 4443-4450. 10.1038/sj.emboj.7600422.PubMed CentralView ArticlePubMedGoogle Scholar
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