PDBsum entry 3c16

Go to PDB code: 
protein ligands metals Protein-protein interface(s) links
Lyase/lyase inhibitor PDB id
Protein chains
190 a.a. *
186 a.a. *
331 a.a. *
_CA ×2
Waters ×6
* Residue conservation analysis
PDB id:
Name: Lyase/lyase inhibitor
Title: Complex of gs-alpha with the catalytic domains of mammalian cyclase: complex with adenosine-5'-triphosphate and ca
Structure: Adenylate cyclase type 5. Chain: a. Fragment: c1a domain. Synonym: adenylate cyclase type v, atp pyrophosphate-lyase adenylyl cyclase 5, ca2+, -inhibitable adenylyl cyclase. Engineered: yes. Mutation: yes. Adenylate cyclase type 2. Chain: b.
Source: Canis lupus familiaris. Dog. Organism_taxid: 9615. Gene: adcy5. Expressed in: escherichia coli. Expression_system_taxid: 562. Rattus norvegicus. Rat. Organism_taxid: 10116.
2.87Å     R-factor:   0.252     R-free:   0.299
Authors: T.-C.Mou,S.R.Sprang
Key ref: T.C.Mou et al. (2009). Structural basis for inhibition of mammalian adenylyl cyclase by calcium. Biochemistry, 48, 3387-3397. PubMed id: 19243146
22-Jan-08     Release date:   03-Feb-09    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P30803  (ADCY5_CANFA) -  Adenylate cyclase type 5
1265 a.a.
190 a.a.*
Protein chain
Pfam   ArchSchema ?
P26769  (ADCY2_RAT) -  Adenylate cyclase type 2
1090 a.a.
186 a.a.
Protein chain
Pfam   ArchSchema ?
P04896  (GNAS2_BOVIN) -  Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
394 a.a.
331 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: Chains A, B: E.C.  - Adenylate cyclase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP = 3',5'-cyclic AMP + diphosphate
Bound ligand (Het Group name = ATP)
corresponds exactly
3',5'-cyclic AMP
Bound ligand (Het Group name = GSP)
matches with 68.75% similarity
+ diphosphate
      Cofactor: Pyridoxal 5'-phosphate
Pyridoxal 5'-phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   3 terms 
  Biological process     intracellular signal transduction   27 terms 
  Biochemical function     nucleotide binding     8 terms  


Biochemistry 48:3387-3397 (2009)
PubMed id: 19243146  
Structural basis for inhibition of mammalian adenylyl cyclase by calcium.
T.C.Mou, N.Masada, D.M.Cooper, S.R.Sprang.
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.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21239683 C.Toyoshima, S.Yonekura, J.Tsueda, and S.Iwasawa (2011).
Trinitrophenyl derivatives bind differently from parent adenine nucleotides to Ca2+-ATPase in the absence of Ca2+.
  Proc Natl Acad Sci U S A, 108, 1833-1838.
PDB codes: 3ar2 3ar3 3ar4 3ar5 3ar6 3ar7 3ar8 3ar9
21059936 S.J.Hyde, B.E.Eckenroth, B.A.Smith, W.A.Eberley, N.H.Heintz, J.E.Jackman, and S.Doublié (2010).
tRNA(His) guanylyltransferase (THG1), a unique 3'-5' nucleotidyl transferase, shares unexpected structural homology with canonical 5'-3' DNA polymerases.
  Proc Natl Acad Sci U S A, 107, 20305-20310.
PDB codes: 3otb 3otc 3otd 3ote
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.