PMID- 21639146 OWN - NLM STAT- MEDLINE DCOM- 20110909 LR - 20211020 IS - 1520-4995 (Electronic) IS - 0006-2960 (Print) IS - 0006-2960 (Linking) VI - 50 IP - 26 DP - 2011 Jul 5 TI - Oxidation and loss of heme in soluble guanylyl cyclase from Manduca sexta. PG - 5813-5 LID - 10.1021/bi200794c [doi] AB - Oxidation and loss of heme in soluble guanylyl/guanylate cyclase (sGC), the nitric oxide receptor, is thought to be a major contributor to cardiovascular disease and is the target of compounds BAY 58-2667 and HMR1766. Using spectroelectrochemical titration, we found a truncated sGC to be highly stable in the ferrous state (234 mV) and to bind ferrous heme tightly even in the presence of NO, despite the NO-induced release of the proximal histidine. In contrast, oxidized sGC readily loses ferric heme to myoglobin (0.47 +/- 0.02 h(-1)). Peroxynitrite, the presumed cellular oxidant, readily oxidizes sGC in 5 mM glutathione. FAU - Fritz, Bradley G AU - Fritz BG AD - Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona 85721, United States. FAU - Hu, Xiaohui AU - Hu X FAU - Brailey, Jacqueline L AU - Brailey JL FAU - Berry, Robert E AU - Berry RE FAU - Walker, F Ann AU - Walker FA FAU - Montfort, William R AU - Montfort WR LA - eng GR - R01 HL054826/HL/NHLBI NIH HHS/United States GR - T32 GM008804/GM/NIGMS NIH HHS/United States GR - R01 HL054826-14/HL/NHLBI NIH HHS/United States GR - HL054826/HL/NHLBI NIH HHS/United States GR - R01 GM077390/GM/NIGMS NIH HHS/United States GR - R01 HL062969/HL/NHLBI NIH HHS/United States GR - HL062969/HL/NHLBI NIH HHS/United States GR - R01 HL062969-11/HL/NHLBI NIH HHS/United States GR - R01 GM077390-04/GM/NIGMS NIH HHS/United States GR - GM077390/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20110610 PL - United States TA - Biochemistry JT - Biochemistry JID - 0370623 RN - 0 (Receptors, Cytoplasmic and Nuclear) RN - 42VZT0U6YR (Heme) RN - EC 4.6.1.2 (Guanylate Cyclase) RN - EC 4.6.1.2 (Soluble Guanylyl Cyclase) SB - IM MH - Animals MH - Guanylate Cyclase/*chemistry/*metabolism MH - Heme/*metabolism MH - Kinetics MH - Manduca/*enzymology MH - Oxidation-Reduction MH - Receptors, Cytoplasmic and Nuclear/*chemistry/*metabolism MH - Soluble Guanylyl Cyclase PMC - PMC3128461 MID - NIHMS302625 EDAT- 2011/06/07 06:00 MHDA- 2011/09/10 06:00 PMCR- 2012/07/05 CRDT- 2011/06/07 06:00 PHST- 2011/06/07 06:00 [entrez] PHST- 2011/06/07 06:00 [pubmed] PHST- 2011/09/10 06:00 [medline] PHST- 2012/07/05 00:00 [pmc-release] AID - 10.1021/bi200794c [doi] PST - ppublish SO - Biochemistry. 2011 Jul 5;50(26):5813-5. doi: 10.1021/bi200794c. Epub 2011 Jun 10.