1pk0

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Revision as of 16:37, 12 November 2007

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spinqualitylabelsall models 1pk0, resolution 3.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal Structure of the EF3-CaM complexed with PMEApp

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

Edema factor (EF), a key virulence factor in anthrax pathogenesis, has, calmodulin (CaM)-activated adenylyl cyclase activity. We have found that, adefovir dipivoxil, a drug approved to treat chronic infection of, hepatitis B virus, effectively inhibits EF-induced cAMP accumulation and, changes in cytokine production in mouse primary macrophages. Adefovir, diphosphate (PMEApp), the active cellular metabolite of adefovir, dipivoxil, inhibits the adenylyl cyclase activity of EF in vitro with high, affinity (K(i) = 27 nM). A crystal structure of EF-CaM-PMEApp reveals that, the catalytic site of EF forms better van der Waals contacts and more, hydrogen bonds with PMEApp than with its endogenous substrate, ATP, providing an explanation for the approximately 10,000-fold higher affinity, EF-CaM has for PMEApp versus ATP. Adefovir dipivoxil is a clinically, approved drug that can block the action of an anthrax toxin. It can be, used to address the role of EF in anthrax pathogenesis.

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

1PK0 is a Protein complex structure of sequences from Bacillus anthracis and Homo sapiens with CA, YB and EMA as ligands. Active as Adenylate cyclase, with EC number 4.6.1.1 Full crystallographic information is available from OCA.

Reference

Selective inhibition of anthrax edema factor by adefovir, a drug for chronic hepatitis B virus infection., Shen Y, Zhukovskaya NL, Zimmer MI, Soelaiman S, Bergson P, Wang CR, Gibbs CS, Tang WJ, Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):3242-7. Epub 2004 Feb 20. PMID:14978283

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