Document Detail

Methylthioadenosine deaminase in an alternative quorum sensing pathway in Pseudomonas aeruginosa.
MedLine Citation:
PMID:  23050701     Owner:  NLM     Status:  MEDLINE    
Pseudomonas aeruginosa possesses an unusual pathway for 5'-methylthioadenosine (MTA) metabolism involving deamination to 5'-methylthioinosine (MTI) followed by N-ribosyl phosphorolysis to hypoxanthine and 5-methylthio-α-d-ribose 1-phosphate. The specific MTI phosphorylase of P. aeruginosa has been reported [Guan, R., Ho, M. C., Almo, S. C., and Schramm, V. L. (2011) Biochemistry 50, 1247-1254], and here we characterize MTA deaminase from P. aeruginosa (PaMTADA). Genomic analysis indicated the PA3170 locus to be a candidate for MTA deaminase (MTADA). Protein encoded by PA3170 was expressed and shown to deaminate MTA with 40-fold greater catalytic efficiency for MTA than for adenosine. The k(cat)/K(m) value of 1.6 × 10(7) M(-1) s(-1) for MTA is the highest catalytic efficiency known for an MTA deaminase. 5'-Methylthiocoformycin (MTCF) is a 4.8 pM transition state analogue for PaMTADA but causes no significant inhibition of human adenosine deaminase or MTA phosphorylase. MTCF is permeable to P. aeruginosa and exhibits an IC(50) of 3 nM on cellular PaMTADA activity. PaMTADA is the only activity in P. aeruginosa extracts to act on MTA. MTA and 5-methylthio-α-d-ribose are involved in quorum sensing pathways; thus, PaMTADA is a potential target for quorum sensing. The crystal structure of PaMTADA in complex with MTCF shows the transition state mimic 8(R)-hydroxyl group in contact with a catalytic site Zn(2+), the 5'-methylthio group in a hydrophobic pocket, and the transition state mimic of the diazepine ring in contact with a catalytic site Glu.
Rong Guan; Meng-Chiao Ho; Richard F G Fröhlich; Peter C Tyler; Steven C Almo; Vern L Schramm
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-11-02
Journal Detail:
Title:  Biochemistry     Volume:  51     ISSN:  1520-4995     ISO Abbreviation:  Biochemistry     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2013-02-07     Completed Date:  2013-02-21     Revised Date:  2013-12-04    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  9094-103     Citation Subset:  IM    
Data Bank Information
Bank Name/Acc. No.:
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Adenosine Deaminase / metabolism
Amino Acid Sequence
Coformycin / analogs & derivatives,  pharmacology
Crystallography, X-Ray
Deoxyadenosines / metabolism*
Methylthioinosine / metabolism
Models, Molecular
Molecular Sequence Data
Nucleoside Deaminases / antagonists & inhibitors,  metabolism*
Pseudomonas aeruginosa / enzymology*
Quorum Sensing*
Sequence Alignment
Substrate Specificity
Thionucleosides / metabolism*
Grant Support
Reg. No./Substance:
0/Deoxyadenosines; 0/Thionucleosides; 11033-22-0/Coformycin; 342-69-8/Methylthioinosine; 634Z2VK3UQ/5'-methylthioadenosine; EC 3.5.4.-/Nucleoside Deaminases; EC 3.5.4.-/methylthioadenosine deaminase, Pseudomonas aeruginosa; EC protein, human; EC Deaminase; EC 6.-/Ligases; EC 6.1.-/N-acylhomoserine lactone synthase

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

Previous Document:  A bactericidal guanidinomethyl biaryl that alters the dynamics of bacterial FtsZ polymerization.
Next Document:  PTT functional recovery in early stage II PTTD after tendon balancing and calcaneal lengthening oste...