PMID- 22426988
OWN - NLM
STAT- MEDLINE
DCOM- 20120918
LR  - 20211021
IS  - 1432-1327 (Electronic)
IS  - 0949-8257 (Linking)
VI  - 17
IP  - 5
DP  - 2012 Jun
TI  - Structural and functional insights into the heme-binding domain of the human 
      soluble guanylate cyclase alpha2 subunit and heterodimeric alpha2beta1.
PG  - 719-30
LID - 10.1007/s00775-012-0891-2 [doi]
AB  - Soluble guanylate cyclase (sGC) mediates NO signaling for a wide range of 
      physiological effects in the cardiovascular system and the central nervous 
      system. The alpha1beta1 isoform is ubiquitously distributed in cytosolic fractions of 
      tissues, whereas alpha2beta1 is mainly found in the brain. The major occurrence and the 
      unique characteristic of human sGC alpha2beta1 indicate a special role in the mediation 
      of neuronal communication. We have efficiently purified and characterized the 
      recombinant heme-binding domain of the human sGC alpha2 subunit (hsGC alpha2(H)) and 
      heterodimeric alpha2beta1 (hsGC beta1(H)-alpha2(H)) by UV-vis spectroscopy, circular dichrosim 
      spectroscopy, EPR spectroscopy, and homology modeling. The heme dissociation and 
      related NO/CO binding/dissociation of both hsGC alpha2(H) and hsGC beta1(H)-alpha2(H) were 
      investigated. The two truncated proteins interact with heme noncovalently. The CO 
      binding affinity of hsGC alpha2(H) is threefold greater than that of human sGC alpha1(H), 
      whereas the dissociation constant k (1) for dissociation of NO from hsGC alpha2(H) is 
      sevenfold larger than that for dissociation of NO from hsGC alpha1(H), although k (2) 
      is almost identical. The results indicate that in comparison with the alpha1beta1 
      isoform, the brain alpha2beta1 isoform exhibits a distinctly different CO/NO affinity 
      and binding rate in favor of NO signaling, and this is consistent with its 
      physiological role in the activation and desensitization. Molecular modeling and 
      sequence alignments are consistent with the hypothesis that His105 contributes to 
      the different CO/NO binding properties of different isoforms. This valuable 
      information is helpful to understand the molecular mechanism by which human sGC 
      alpha2beta1 mediates NO/CO signaling.
FAU - Wang, Hongyan
AU  - Wang H
AD  - Institutes of Biomedical Sciences, Fudan University, Shanghai, 200433, China.
FAU - Zhong, Fangfang
AU  - Zhong F
FAU - Pan, Jie
AU  - Pan J
FAU - Li, Wei
AU  - Li W
FAU - Su, Jihu
AU  - Su J
FAU - Huang, Zhong-Xian
AU  - Huang ZX
FAU - Tan, Xiangshi
AU  - Tan X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120318
PL  - Germany
TA  - J Biol Inorg Chem
JT  - Journal of biological inorganic chemistry : JBIC : a publication of the Society 
      of Biological Inorganic Chemistry
JID - 9616326
RN  - 0 (Protein Subunits)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 7U1EE4V452 (Carbon Monoxide)
RN  - EC 4.6.1.2 (Guanylate Cyclase)
RN  - EC 4.6.1.2 (Soluble Guanylyl Cyclase)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Carbon Monoxide/metabolism
MH  - Cloning, Molecular
MH  - Guanylate Cyclase/*chemistry/genetics/*metabolism
MH  - Humans
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Nitric Oxide/metabolism
MH  - Protein Subunits/chemistry/metabolism
MH  - Receptors, Cytoplasmic and Nuclear/*chemistry/genetics/*metabolism
MH  - Sequence Alignment
MH  - Soluble Guanylyl Cyclase
EDAT- 2012/03/20 06:00
MHDA- 2012/09/19 06:00
CRDT- 2012/03/20 06:00
PHST- 2011/12/24 00:00 [received]
PHST- 2012/03/05 00:00 [accepted]
PHST- 2012/03/20 06:00 [entrez]
PHST- 2012/03/20 06:00 [pubmed]
PHST- 2012/09/19 06:00 [medline]
AID - 10.1007/s00775-012-0891-2 [doi]
PST - ppublish
SO  - J Biol Inorg Chem. 2012 Jun;17(5):719-30. doi: 10.1007/s00775-012-0891-2. Epub 
      2012 Mar 18.