1ykd
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Crystal Structure of the Tandem GAF Domains from a Cyanobacterial Adenylyl Cyclase: Novel Modes of Ligand-Binding and Dimerization
OverviewOverview
In several species, GAF domains, which are widely expressed, small-molecule-binding domains that regulate enzyme activity, are known to, bind cyclic nucleotides. However, the molecular mechanism by which cyclic, nucleotide binding affects enzyme activity is not known for any GAF, domain. In the cyanobacterium, Anabaena, the cyaB1 and cyaB2 genes encode, adenylyl cyclases that are stimulated by binding of cAMP to their, N-terminal GAF domains. Replacement of the tandem GAF-A/B domains in cyaB1, with the mammalian phosphodiesterase 2A GAF-A/B tandem domains allows, regulation of the chimeric protein by cGMP, suggesting a highly conserved, mechanism of activation. Here, we describe the 1.9-A crystal structure of, the tandem GAF-A/B domains of cyaB2 with bound cAMP and compare it to the, previously reported structure of the PDE2A GAF-A/B. Unexpectedly, the, cyaB2 GAF-A/B dimer is antiparallel, unlike the parallel dimer of PDE2A., Moreover, there is clear electron density for cAMP in both GAF-A and -B, whereas in PDE2A, cGMP is found only in GAF-B. Phosphate and ribose group, contacts are similar to those in PDE2A. However, the purine-binding, pockets appear very different from that in PDE2A GAF-B. Differences in the, beta2-beta3 loop suggest that this loop confers much of the ligand, specificity in this and perhaps in many other GAF domains. Finally, a, conserved asparagine appears to be a new addition to the signature NKFDE, motif, and a mechanism for this motif to stabilize the cNMP-binding pocket, is proposed.
About this StructureAbout this Structure
1YKD is a Single protein structure of sequence from Anabaena sp. with CMP as ligand. Active as Adenylate cyclase, with EC number 4.6.1.1 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of the tandem GAF domains from a cyanobacterial adenylyl cyclase: modes of ligand binding and dimerization., Martinez SE, Bruder S, Schultz A, Zheng N, Schultz JE, Beavo JA, Linder JU, Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):3082-7. Epub 2005 Feb 11. PMID:15708973
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