PDBsum entry: 1azs

Complex (lyase/hydrolase)

PDB-id: 1azs

Asymmetric unit

Contents

Description

Header details

Header records

References

PROCHECK

Protein chains

190 a.a. *

189 a.a. *

339 a.a. *

Ligands

FKP

GSP

Metal ions

_MG

Waters ×69

* Residue conservation analysis

Tools

Clefts Calculation

Biological unit*, hexamer
(*as deduced by PQS)

PDB id:

1azs

Name:

Complex (lyase/hydrolase)

Title:

Complex of gs-alpha with the catalytic domains of mammalian adenylyl cyclase

Structure:

Vc1. Chain: a. Fragment: c1a domain of adenylyl cyclase. Engineered: yes. Mutation: yes. Iic2. Chain: b. Fragment: c2a domain of adenylyl cyclase. Engineered: yes.

Source:

Canis lupus familiaris. Dog. Organism_taxid: 9615. Strain: familiaris. Organ: plasma. Tissue: cardiac muscle. Cellular_location: plasma membrane. Gene: adenylyl cyclase type v. Expressed in: escherichia coli bl21(de3).

Biological unit:

Hexamer (from PQS)

UniProt:

Chain A: P30803 (ADCY5_CANFA)

Seq:
Struc:
	Seq:
	Struc:
Seq:
Struc:
	Seq:
	Struc:
Seq:		1265 a.a.
Struc:		190 a.a.*

Chain B: P26769 (ADCY2_RAT)

Seq:
Struc:
	Seq:
	Struc:
Seq:
Struc:
	Seq:
	Struc:
Seq:		1090 a.a.
Struc:		189 a.a.

Chain C: P04896 (GNAS2_BOVIN)

Seq:

Struc:

Seq:

394 a.a.

Struc:

339 a.a.

Key:	PfamA domain
Secondary structure	CATH domain

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme class:

Chains A, B: E.C.4.6.1.1   [IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Reaction:

ATP = 3',5'-cyclic AMP + diphosphate (see diagram below)

Cofactor:

Pyridoxal-phosphate

Resolution:

2.30Å

R-factor:

0.219

R-free:

0.282

Authors:

J.J.G.Tesmer,S.R.Sprang

Key ref:

J.J.Tesmer et al. (1997). Crystal structure of the catalytic domains of adenylyl cyclase in a complex with Gsalpha.GTPgammaS.. Science, 278, 1907-1916. [PubMed id: 9417641] [DOI: 10.1126/science.278.5345.1907]

Date:

20-Nov-97

Release date:

25-Feb-98

Quick_links

Procheck

Surface

Key reference

DOI no: 10.1126/science.278.5345.1907

Science 278:1907-1916 (1997)

PubMed id: 9417641

Crystal structure of the catalytic domains of adenylyl cyclase in a complex with Gsalpha.GTPgammaS.

J.J.Tesmer, R.K.Sunahara, A.G.Gilman, S.R.Sprang.

ABSTRACT

The crystal structure of a soluble, catalytically active form of adenylyl cyclase in a complex with its stimulatory heterotrimeric G protein alpha subunit (Gsalpha) and forskolin was determined to a resolution of 2.3 angstroms. When P-site inhibitors were soaked into native crystals of the complex, the active site of adenylyl cyclase was located and structural elements important for substrate recognition and catalysis were identified. On the basis of these and other structures, a molecular mechanism is proposed for the activation of adenylyl cyclase by Gsalpha.

Selected figure(s)

Figure 1.
Fig. 1. Architecture of the heterodimeric complex between VC[1] (mauve) and IIC[2] (khaki) bound to the forskolin analog MPFsk, as observed^ in the complex with G[s][ ]·GTP S. (A) View along the pseudo-twofold^ axis toward the ventral surface of VC[1]·IIC[2]. The forskolin derivative^ is shown as a stick figure: carbon, gray; nitrogen, cyan; and^ oxygen, red. N and C mark the first and last ordered residues^ in the crystal structure of the heterodimer. (B) VC[1] is^ depicted side-by-side with a molecule of IIC[2] that has been superimposed^ on VC[1] (rmsd of 1.3 Å for 153 C atom pairs). Elements of secondary^ structure are labeled; in all of the figures, the color of the^ label identifies the protein subunit to which it refers. (C)^ Stereo diagram of the VC[1]·IIC[2] interface, with the C backbone^ depicted as a continuous tube. The view is the same as in (A).^ Ball-and-stick models of C C bonds are shown for residues (50)^ that participate in interdomain contacts (separated by less than^ 4 Å from an atom in the opposite domain). These residues constitute^ the subset of interfacial residues that are conserved in all adenylyl^ cyclase isoforms. C atoms of residues with acidic side chains^ are red, basic residues are blue, and residues with polar side^ chains are pink. The C atoms of nonpolar residues are khaki (VC[1])^ or mauve (IIC[2]). Dashed gray lines show interdomain side chain-side^ chain or side chain-main chain hydrogen bonds or ion pairs involving^ polar or charged interfacial residues. Only the polar or charged^ residues are labeled.

Figure 3.
Fig. 3. Only one molecule of forskolin binds in the ventral cleft of VC[1]·IIC[2]. MPFsk binds in the ventral cleft of adenylyl cyclase^ at the end closest to the G[s][ ]binding site and is drawn in^ green without its methyl-piperazino group for clarity. Residues^ constituting the forskolin binding site of the IIC[2] homodimer^ (14) that differ from their equivalents in the binding site^ of VC[1]·IIC[2] are drawn in transparent rose (50). The side chain^ of Trp^1020 is also shown because its side chain adopts a dramatically different^ conformation from that of Trp^507 in the VC[1]·IIC[2] heterodimer. To generate this figure, we superimposed^ one of the forskolin molecules from the IIC[2] homodimer with MPFsk;^ this superposition does not optimally align the protein subunits^ of each structure.

The above figures are reprinted by permission from the AAAs: Science (1997, 278, 1907-1916) copyright 1997.

Figures were selected by the author.