PMID- 6120166
OWN - NLM
STAT- MEDLINE
DCOM- 19820420
LR  - 20210210
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 257
IP  - 3
DP  - 1982 Feb 10
TI  - Effect of GTP analogues on purified soluble guanylate cyclase.
PG  - 1309-11
AB  - In our studies with purified soluble guanylate cyclase from rat lung, we have 
      tested a number of guanosine 5'-triphosphate (GTP) analogues as substrates and 
      inhibitors, 5'-Guanylylimidodiphosphate (GMP-P(NH)P), guanylyl (beta, 
      gamma-methylene) diphosphate (GMP-P(CH2)P), and guanosine 
      5'-O-(3-thiotriphosphate) (GTP gamma S) were found to be substrates for guanylate 
      cyclase. GTP gamma S supported cyclic GMP formation at 20 or 75% of the rate seen 
      with Mn2+-GTP and Mg2+-GTP, respectively. GMP-P(NH)P and GMP P(CH2)P supported 
      cyclic GMP formation at 10-20% of the GTP rate with either cation cofactor. These 
      analogues were found to have multiple Km values; one Km value was similar to GTP 
      (150 microM with Mg2+, 20-70 microM with Mn2+), but an additional high affinity 
      catalytic site (3 microM) was also observed. Guanosine tetraphosphate (Ki = 10 
      microM), adenosine triphosphate (Ki = 9 microM) and the 2'3'-dialdehyde 
      derivative of GTP (dial GTP) (Ki = 1 microM) were not good substrates for the 
      enzyme; however, they were potent competitive inhibitors. These GTP analogues 
      will be useful tools for the study of GTP binding sites on guanylate cyclase and 
      they may also help elucidate the effects of free radicals and other agents on 
      guanylate cyclase regulation.
FAU - Brandwein, H J
AU  - Brandwein HJ
FAU - Lewicki, J A
AU  - Lewicki JA
FAU - Waldman, S A
AU  - Waldman SA
FAU - Murad, F
AU  - Murad F
LA  - eng
GR  - AM15316/AM/NIADDK NIH HHS/United States
GR  - GM7500/GM/NIGMS NIH HHS/United States
GR  - HL18260/HL/NHLBI NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Ribonucleotides)
RN  - 86-01-1 (Guanosine Triphosphate)
RN  - EC 4.6.1.2 (Guanylate Cyclase)
SB  - IM
MH  - Animals
MH  - Guanosine Triphosphate/*analogs & derivatives/pharmacology
MH  - Guanylate Cyclase/isolation & purification/*metabolism
MH  - Kinetics
MH  - Lung/enzymology
MH  - Rats
MH  - Ribonucleotides/pharmacology
MH  - Substrate Specificity
EDAT- 1982/02/10 00:00
MHDA- 1982/02/10 00:01
CRDT- 1982/02/10 00:00
PHST- 1982/02/10 00:00 [pubmed]
PHST- 1982/02/10 00:01 [medline]
PHST- 1982/02/10 00:00 [entrez]
AID - S0021-9258(19)68192-5 [pii]
PST - ppublish
SO  - J Biol Chem. 1982 Feb 10;257(3):1309-11.