Predicted structures of the cGMP binding domains of the cGMP-dependent protein kinase: a key alanine/threonine difference in evolutionary divergence of cAMP and cGMP binding sites.

Abstract:

:Mammalian cGMP- and cAMP-dependent protein kinase show considerable similarity in amino acid sequence, although they specifically bind different cyclic nucleotides. Results of cGMP analogue binding experiments, combined with modeling of the cGMP binding sites by analogy to the structure of the homologous catabolite gene activator protein, suggest that a threonine residue forms a hydrogen bond with the 2-NH2 of cGMP. This threonine is invariant in all cGMP binding domains, but the corresponding residue in 23 out of 24 cAMP binding sites of protein kinases is alanine, which cannot form the same hydrogen bond. This alanine/threonine difference has the potential for discriminating between cAMP and cGMP and may be important in the evolutionary divergence of cyclic nucleotide binding sites.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Weber IT,Shabb JB,Corbin JD

doi

10.1021/bi00440a059

subject

Has Abstract

pub_date

1989-07-11 00:00:00

pages

6122-7

issue

14

eissn

0006-2960

issn

1520-4995

journal_volume

28

pub_type

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