3C14

Complex of GS-Alpha with the Catalytic Domains of Mammalian Adenylyl Cyclase: Complex with Pyrophosphate and Ca

3C14 の概要

• エントリーDOI: 10.2210/pdb3c14/pdb
• 関連するPDBエントリー: 3C15 3C16
• 分子名称: Adenylate cyclase type 5, Adenylate cyclase type 2, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, ... (10 entities in total)
• 機能のキーワード: adenylyl cyclase, gsalpha, pyrophosphate, camp biosynthesis, glycoprotein, lyase, magnesium, membrane, metal-binding, phosphoprotein, transmembrane, gtp-binding, lipoprotein, nucleotide-binding, palmitate, transducer, lyase-lyase inhibitor complex, lyase/lyase inhibitor
• 由来する生物種: Canis lupus familiaris (Dog); 詳細
• 細胞内の位置: Membrane; Multi-pass membrane protein: P30803 P26769; Cell membrane; Lipid-anchor (By similarity): P04896
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 97181.59

構造登録者

Mou, T.-C.,Sprang, S.R. (登録日: 2008-01-22, 公開日: 2009-02-03, 最終更新日: 2023-08-30)

主引用文献

Mou, T.C.,Masada, N.,Cooper, D.M.,Sprang, S.R.
Structural basis for inhibition of mammalian adenylyl cyclase by calcium.
Biochemistry, 48:3387-3397, 2009

PubMed Abstract: Type V and VI mammalian adenylyl cyclases (AC5, AC6) are inhibited by Ca(2+) at both sub- and supramicromolar concentration. This inhibition may provide feedback in situations where cAMP promotes opening of Ca(2+) channels, allowing fine control of cardiac contraction and rhythmicity in cardiac tissue where AC5 and AC6 predominate. Ca(2+) inhibits the soluble AC core composed of the C1 domain of AC5 (VC1) and the C2 domain of AC2 (IIC2). As observed for holo-AC5, inhibition is biphasic, showing "high-affinity" (K(i) = approximately 0.4 microM) and "low-affinity" (K(i) = approximately 100 microM) modes of inhibition. At micromolar concentration, Ca(2+) inhibition is nonexclusive with respect to pyrophosphate (PP(i)), a noncompetitive inhibitor with respect to ATP, but at >100 microM Ca(2+), inhibition appears to be exclusive with respect to PP(i). The 3.0 A resolution structure of Galphas.GTPgammaS/forskolin-activated VC1:IIC2 crystals soaked in the presence of ATPalphaS and 8 microM free Ca(2+) contains a single, loosely coordinated metal ion. ATP soaked into VC1:IIC2 crystals in the presence of 1.5 mM Ca(2+) is not cyclized, and two calcium ions are observed in the 2.9 A resolution structure of the complex. In both of the latter complexes VC1:IIC2 adopts the "open", catalytically inactive conformation characteristic of the apoenzyme, in contrast to the "closed", active conformation seen in the presence of ATP analogues and Mg(2+) or Mn(2+). Structures of the pyrophosphate (PP(i)) complex with 10 mM Mg(2+) (2.8 A) or 2 mM Ca(2+) (2.7 A) also adopt the open conformation, indicating that the closed to open transition occurs after cAMP release. In the latter complexes, Ca(2+) and Mg(2+) bind only to the high-affinity "B" metal site associated with substrate/product stabilization. Ca(2+) thus stabilizes the inactive conformation in both ATP- and PP(i)-bound states.

PubMed: 19243146
DOI: 10.1021/bi802122k

実験手法

X-RAY DIFFRACTION (2.68 Å)