PDBsum entry 1s26

Toxin,lyase/metal binding protein

PDB id: 1s26

Contents

Protein chains

485 a.a.

143 a.a. *

Ligands

APC ×3

Metals

_CA ×6

_YB ×3

* Residue conservation analysis

PDB id:

1s26

Name:

Toxin,lyase/metal binding protein

Title:

Structure of anthrax edema factor-calmodulin-alpha,beta- methyleneadenosine 5'-triphosphate complex reveals an alternative mode of atp binding to the catalytic site

Structure:

Calmodulin-sensitive adenylate cyclase. Chain: a, b, c. Fragment: residue 291-800, c-terminal ef3. Synonym: atp pyrophosphate-lyase, adenylyl cyclase, edema factor, ef, anthrax edema toxin adenylate cyclase component. Engineered: yes. Calmodulin. Chain: d, e, f. Engineered: yes

Source:

Bacillus anthracis. Organism_taxid: 1392. Gene: cya, pxo1-122. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Homo sapiens. Human. Organism_taxid: 9606. Gene: calm1, cam1, calm, cam , calm2, cam2, camb , calm3, cam3,

Biol. unit:

Dimer (from PQS)

Resolution:

3.00Å R-factor: 0.264 R-free: 0.304

Authors:

Y.Shen,N.L.Zhukovskaya,A.Bohm,W.-J.Tang

Key ref:

Y.Shen et al. (2004). Structure of anthrax edema factor-calmodulin-adenosine 5'-(alpha,beta-methylene)-triphosphate complex reveals an alternative mode of ATP binding to the catalytic site. Biochem Biophys Res Commun, 317, 309-314. PubMed id: 15063758 DOI: 10.1016/j.bbrc.2004.03.046

Date:

08-Jan-04 Release date: 13-Apr-04

Protein chains

P40136  (CYAA_BACAN) -  Calmodulin-sensitive adenylate cyclase from Bacillus anthracis

Seq: 800 a.a.

Struc: 485 a.a.

Protein chains

P0DP23  (CALM1_HUMAN) -  Calmodulin-1 from Homo sapiens

Seq: 149 a.a.

Struc: 143 a.a.

Enzyme reactions

• Enzyme class: Chains A, B, C: E.C.4.6.1.1 - adenylate cyclase.
• Reaction: ATP = 3',5'-cyclic AMP + diphosphate

ATP = 3',5'-cyclic AMP (Bound ligand (Het Group name = APC) matches with 70.97% similarity) + diphosphate

• Cofactor: Pyridoxal 5'-phosphate

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/j.bbrc.2004.03.046

Biochem Biophys Res Commun 317:309-314 (2004)

PubMed id: 15063758

Structure of anthrax edema factor-calmodulin-adenosine 5'-(alpha,beta-methylene)-triphosphate complex reveals an alternative mode of ATP binding to the catalytic site.

Y.Shen, Q.Guo, N.L.Zhukovskaya, C.L.Drum, A.Bohm, W.J.Tang.

ABSTRACT

Anthrax edema factor (EF) is a key virulence factor secreted by Bacillus anthracis. Here, we report a structure, at 3.0 A resolution, of the catalytic domain of EF (EF3) in complex with calmodulin (CaM) and adenosine 5'-(alpha,beta-methylene)-triphosphate (AMPCPP). Although the binding of the triphosphate of AMPCPP to EF3 can be superimposed on that of previously determined 3'deoxy-ATP (3'dATP) and 2'deoxy 3' anthraniloyl-ATP (2'd3' ANT-ATP) in EF3-CaM, the ribose and the adenine rings of AMPCPP are rotated approximately 105 and 180 degrees, respectively, relative to those of 3'dATP and 2'd3'ANT-ATP. Based on this model, K382 and F586 should play key roles in the recognition of adenine. However, mutations of these residues to alanine either separately or together cause only modest changes in Michaelis-Menten constants and IC50 values of AMPCPP and cAMP. Therefore, this alternate binding mode of the adenosine of AMPCPP binds to EF likely playing only a minor role in ATP binding and in catalysis.