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Titolo:
The amino-terminal cyclic nucleotide binding site of the type II cGMP-dependent protein kinase is essential for full cyclic nucleotide-dependent activation
Autore:
Taylor, MK; Uhler, MD;
Indirizzi:
Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48104 USA Univ Michigan Ann Arbor MI USA 48104 t Biol Chem, Ann Arbor, MI 48104 USA Univ Michigan, Grad Program Neurosci, Ann Arbor, MI 48104 USA Univ Michigan Ann Arbor MI USA 48104 am Neurosci, Ann Arbor, MI 48104 USA Univ Michigan, Mental Hlth Res Inst, Ann Arbor, MI 48104 USA Univ Michigan Ann Arbor MI USA 48104 th Res Inst, Ann Arbor, MI 48104 USA
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 36, volume: 275, anno: 2000,
pagine: 28053 - 28062
SICI:
0021-9258(20000908)275:36<28053:TACNBS>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
REGULATORY SUBUNIT; CAMP BINDING; CATALYTIC SUBUNIT; GMP; AMP; EXPRESSION; ALPHA; MUTATIONS; DISTINCT; DOMAINS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
58
Recensione:
Indirizzi per estratti:
Indirizzo: Uhler, MD Univ Michigan, Dept Biol Chem, Neurosci Labs Bldg,1103 E Huron St, Ann Arbor, MI 48104 USA Univ Michigan Neurosci Labs Bldg,1103 E Huron StAnn Arbor MI USA 48104
Citazione:
M.K. Taylor e M.D. Uhler, "The amino-terminal cyclic nucleotide binding site of the type II cGMP-dependent protein kinase is essential for full cyclic nucleotide-dependent activation", J BIOL CHEM, 275(36), 2000, pp. 28053-28062

Abstract

For the type I cGMP-dependent protein kinases (cGKI alpha and cGKI beta), a high affinity interaction exists between the C2 amino group of cGMP and the hydroxyl side chain of a threonine conserved in most cGMP binding sites. To examine the effect of this interaction on ligand binding and kinase activation in the type II isozyme of cGMP-dependent protein kinase (cGKII), alanine was substituted for the conserved threonine or serine. cGKII was found to require the C2 amino group of cGMP and its cognate serine or threoninehydroxyl for efficient cGMP activation. Of the two binding sites, disruption of cGMP-specific binding in the NH2-terminal binding site had the greatest effect on cGMP-dependent kinase activation, like cGKI. However, ligand dissociation studies showed that the location of the rapid and slow dissociation sites of cGKII was reversed relative to cGKI, Another set of mutationsthat prevented cyclic nucleotide binding demonstrated the necessity of theNH2-terminal, rapid dissociation binding site for cyclic nucleotide-dependent activation of cGKII. These findings suggest distinct mechanisms of activation for cGKII and cGKI isoforms, Because cGKII mediates the effects of heat-stable enterotoxins via the cystic fibrosis transmembrane regulator Cl-channel, these findings define a structural target for drug design.

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Documento generato il 14/07/20 alle ore 19:19:41