Document Detail


A mycobacterial cyclic AMP phosphodiesterase that moonlights as a modifier of cell wall permeability.
MedLine Citation:
PMID:  19801656     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mycobacterium tuberculosis utilizes many mechanisms to establish itself within the macrophage, and bacterially derived cAMP is important in modulating the host cellular response. Although the genome of M. tuberculosis is endowed with a number of mammalian-like adenylyl cyclases, only a single cAMP phosphodiesterase has been identified that can decrease levels of cAMP produced by the bacterium. We present the crystal structure of the full-length and sole cAMP phosphodiesterase, Rv0805, found in M. tuberculosis, whose orthologs are present only in the genomes of slow growing and pathogenic mycobacteria. The dimeric core catalytic domain of Rv0805 adopts a metallophosphoesterase-fold, and the C-terminal region builds the active site and contributes to multiple substrate utilization. Localization of Rv0805 to the cell wall is dependent on its C terminus, and expression of either wild type or mutationally inactivated Rv0805 in M. smegmatis alters cell permeability to hydrophobic cytotoxic compounds. Rv0805 may therefore play a key role in the pathogenicity of mycobacteria, not only by hydrolyzing bacterial cAMP, but also by moonlighting as a protein that can alter cell wall functioning.
Authors:
Marjetka Podobnik; Richa Tyagi; Nishad Matange; Urska Dermol; Arun K Gupta; Rohini Mattoo; Kothandaraman Seshadri; Sandhya S Visweswariah
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-09-29
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  284     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-11-16     Completed Date:  2009-12-14     Revised Date:  2013-05-31    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  32846-57     Citation Subset:  IM    
Affiliation:
Laboratory for Biosynthesis and Biotransformation, National Institute of Chemistry of Slovenia, Hajdrihova 19,1000 Ljubljana, Slovenia. marjetka.podobnik@ki.si
Data Bank Information
Bank Name/Acc. No.:
PDB/3IB7;  3IB8
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MeSH Terms
Descriptor/Qualifier:
3',5'-Cyclic-AMP Phosphodiesterases / physiology*
Amino Acid Sequence
Catalytic Domain
Cell Wall / enzymology,  microbiology*
Crystallography, X-Ray / methods
Culture Media
Cyclic AMP / metabolism
Dimerization
Models, Molecular
Molecular Conformation
Molecular Sequence Data
Mycobacterium tuberculosis / enzymology*
Permeability
Protein Structure, Tertiary
Substrate Specificity
Chemical
Reg. No./Substance:
0/Culture Media; 60-92-4/Cyclic AMP; EC 3.1.4.17/3',5'-Cyclic-AMP Phosphodiesterases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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