1s26

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spinqualitylabelsall models 1s26, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Structure of Anthrax Edema Factor-Calmodulin-alpha,beta-methyleneadenosine 5'-triphosphate Complex Reveals an Alternative Mode of ATP Binding to the Catalytic Site

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

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.

Disease

Known diseases associated with this structure: Cavernous malformations of CNS and retina OMIM:[604214], Cerebral cavernous malformations-1 OMIM:[604214], Hyperkeratotic cutaneous capillary-venous malformations associated with cerebral capillary malformations OMIM:[604214], Leukemia, acute T-cell lymphoblastic OMIM:[603025], Leukemia, acute myeloid OMIM:[603025]

About this Structure

1S26 is a Protein complex structure of sequences from Bacillus anthracis and Homo sapiens with , and as ligands. Active as Adenylate cyclase, with EC number 4.6.1.1 Full crystallographic information is available from OCA.

Reference

Structure of anthrax edema factor-calmodulin-adenosine 5'-(alpha,beta-methylene)-triphosphate complex reveals an alternative mode of ATP binding to the catalytic site., Shen Y, Guo Q, Zhukovskaya NL, Drum CL, Bohm A, Tang WJ, Biochem Biophys Res Commun. 2004 Apr 30;317(2):309-14. PMID:15063758

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