PMID- 29702251
OWN - NLM
STAT- MEDLINE
DCOM- 20190403
LR  - 20211109
IS  - 1089-8611 (Electronic)
IS  - 1089-8603 (Print)
IS  - 1089-8603 (Linking)
VI  - 77
DP  - 2018 Jul 1
TI  - Structure/function of the soluble guanylyl cyclase catalytic domain.
PG  - 53-64
LID - S1089-8603(18)30027-2 [pii]
LID - 10.1016/j.niox.2018.04.008 [doi]
AB  - Soluble guanylyl cyclase (GC-1) is the primary receptor of nitric oxide (NO) in 
      smooth muscle cells and maintains vascular function by inducing vasorelaxation in 
      nearby blood vessels. GC-1 converts guanosine 5'-triphosphate (GTP) into cyclic 
      guanosine 3',5'-monophosphate (cGMP), which acts as a second messenger to improve 
      blood flow. While much work has been done to characterize this pathway, we lack a 
      mechanistic understanding of how NO binding to the heme domain leads to a large 
      increase in activity at the C-terminal catalytic domain. Recent structural 
      evidence and activity measurements from multiple groups have revealed a 
      low-activity cyclase domain that requires additional GC-1 domains to promote a 
      catalytically-competent conformation. How the catalytic domain structurally 
      transitions into the active conformation requires further characterization. This 
      review focuses on structure/function studies of the GC-1 catalytic domain and 
      recent advances various groups have made in understanding how catalytic activity 
      is regulated including small molecules interactions, Cys-S-NO modifications and 
      potential interactions with the NO-sensor domain and other proteins.
CI  - Copyright (c) 2018 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Childers, Kenneth C
AU  - Childers KC
AD  - University of Maryland Baltimore County, Department of Chemistry and 
      Biochemistry, Baltimore, USA.
FAU - Garcin, Elsa D
AU  - Garcin ED
AD  - University of Maryland Baltimore County, Department of Chemistry and 
      Biochemistry, Baltimore, USA. Electronic address: egarcin@umbc.edu.
LA  - eng
GR  - R21 EY026663/EY/NEI NIH HHS/United States
GR  - T32 GM066706/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20180425
PL  - United States
TA  - Nitric Oxide
JT  - Nitric oxide : biology and chemistry
JID - 9709307
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 4.6.1.2 (Soluble Guanylyl Cyclase)
SB  - IM
MH  - Animals
MH  - Biocatalysis
MH  - *Catalytic Domain
MH  - Humans
MH  - Nitric Oxide/metabolism
MH  - Protein Conformation
MH  - Soluble Guanylyl Cyclase/*chemistry/*metabolism
MH  - Structure-Activity Relationship
PMC - PMC6005667
MID - NIHMS973676
OTO - NOTNLM
OT  - Activation mechanism
OT  - Adenylyl cyclase
OT  - Catalytic domain
OT  - Nitric oxide
OT  - S-nitrosation
OT  - Soluble guanylyl cyclase
COIS- Declarations of interest None.
EDAT- 2018/04/28 06:00
MHDA- 2019/04/04 06:00
PMCR- 2018/07/01
CRDT- 2018/04/28 06:00
PHST- 2018/01/31 00:00 [received]
PHST- 2018/04/20 00:00 [revised]
PHST- 2018/04/23 00:00 [accepted]
PHST- 2018/04/28 06:00 [pubmed]
PHST- 2019/04/04 06:00 [medline]
PHST- 2018/04/28 06:00 [entrez]
PHST- 2018/07/01 00:00 [pmc-release]
AID - S1089-8603(18)30027-2 [pii]
AID - 10.1016/j.niox.2018.04.008 [doi]
PST - ppublish
SO  - Nitric Oxide. 2018 Jul 1;77:53-64. doi: 10.1016/j.niox.2018.04.008. Epub 2018 Apr 
      25.