Structural and functional analysis of the pyocyanin biosynthetic protein PhzM from Pseudomonas aeruginosa.

Structural and functional analysis of the pyocyanin biosynthetic protein PhzM from Pseudomonas aeruginosa. Research Abstract Details 

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Structural and functional analysis of the pyocyanin biosynthetic protein PhzM from Pseudomonas aeruginosa. Abstract Text:

James F Parsons,Bryan T Greenhagen,Katherine Shi,Kelly Calabrese,Howard Robinson,Jane E Ladner,

Pyocyanin is a biologically active phenazine produced by the human pathogen Pseudomonas aeruginosa. It is thought to endow P. aeruginosa with a competitive growth advantage in colonized tissue and is also thought to be a virulence factor in diseases such as cystic fibrosis and AIDS where patients are commonly infected by pathogenic Pseudomonads due to their immunocompromised state. Pyocyanin is also a chemically interesting compound due to its unusual oxidation-reduction activity. Phenazine-1-carboxylic acid, the precursor to the bioactive phenazines, is synthesized from chorismic acid by enzymes encoded in a seven-gene cistron in P. aeruginosa and in other Pseudomonads. Phenzine-1-carboxylic acid is believed to be converted to pyocyanin by the sequential actions of the putative S-adenosylmethionine-dependent N-methyltransferase PhzM and the putative flavin-dependent hydroxylase PhzS. Here we report the 1.8 A crystal structure of PhzM determined by single anomalous dispersion. Unlike many methyltransferases, PhzM is a dimer in solution. The 36 kDa PhzM polypeptide folds into three domains. The C-terminal domain exhibits the alpha/beta-hydrolase fold typical of small molecule methyltransferases. Two smaller N-terminal domains form much of the dimer interface. Structural alignments with known methyltransferases show that PhzM is most similar to the plant O-methyltransferases that are characterized by an unusual intertwined dimer interface. The structure of PhzM contains no ligands, and the active site is open and solvent-exposed when compared to structures of similar enzymes. In vitro experiments using purified PhzM alone demonstrate that it has little or no ability to methylate phenzine-1-carboxylic acid. However, when the putative hydroxylase PhzS is included, pyocyanin is readily produced. This observation suggests that a mechanism has evolved in P. aeruginosa that ensures efficient production of pyocyanin via the prevention of the formation and release of an unstable and potentially deleterious intermediate.

Structural and functional analysis of the pyocyanin biosynthetic protein PhzM from Pseudomonas aeruginosa. Publishing Authors By Initials

JF Parsons,BT Greenhagen,K Shi,K Calabrese,H Robinson,JE Ladner,

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Structural and functional analysis of the pyocyanin biosynthetic protein PhzM from Pseudomonas aeruginosa. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Biochemistry

VOLUME: 46

Page Numbers: 1821-8

Journal Abbreviation: Biochemistry

ISSN: 0006-2960

DAY: 25

MONTH: 01

YEAR: 2007

Structural and functional analysis of the pyocyanin biosynthetic protein PhzM from Pseudomonas aeruginosa. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 370623

Structural and functional analysis of the pyocyanin biosynthetic protein PhzM from Pseudomonas aeruginosa. Keywords Mesh Terms:

KEYWORDS: Solutions

MESH TERMS: chemical synthesis

Chemical & Substance for Abstract: Structural and functional analysis of the pyocyanin biosynthetic protein PhzM from Pseudomonas aeruginosa. Information

Substance Name: PhzM protein, Pseudomonas aeruginosa

Registry Number: EC 2.1.1.-

Grant and Affiliation Information for Structural and functional analysis of the pyocyanin biosynthetic protein PhzM from Pseudomonas aeruginosa.

AFFILIATION: Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, Maryland 20850, USA. parsonsj@umbi.umd.edu

Country: United States

AGENCY: United States NIAID

GRANT: AI067530

ACRONYM: AI

MEDLINETA: Biochemistry

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