1YKD

Crystal Structure of the Tandem GAF Domains from a Cyanobacterial Adenylyl Cyclase: Novel Modes of Ligand-Binding and Dimerization

1YKD の概要

• エントリーDOI: 10.2210/pdb1ykd/pdb
• 分子名称: adenylate cyclase, ADENOSINE-3',5'-CYCLIC-MONOPHOSPHATE (3 entities in total)
• 機能のキーワード: gaf domain, bound cyclic amp ligand, lyase
• 由来する生物種: Anabaena sp.
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 91174.30

構造登録者

Martinez, S.E.,Bruder, S.,Schultz, A.,Zheng, N.,Schultz, J.E.,Beavo, J.A.,Linder, J.U. (登録日: 2005-01-17, 公開日: 2005-02-22, 最終更新日: 2024-02-14)

主引用文献

Martinez, S.E.,Bruder, S.,Schultz, A.,Zheng, N.,Schultz, J.E.,Beavo, J.A.,Linder, J.U.
Crystal structure of the tandem GAF domains from a cyanobacterial adenylyl cyclase: Modes of ligand binding and dimerization
Proc.Natl.Acad.Sci.USA, 102:3082-3087, 2005

PubMed Abstract: 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.

PubMed: 15708973
DOI: 10.1073/pnas.0409913102

実験手法

X-RAY DIFFRACTION (1.9 Å)