Analysis of the stoichiometric metal activation of methionine aminopeptidase

Sergio C. Chai, Qizhuang Ye

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background. Methionine aminopeptidase (MetAP) is a ubiquitous enzyme required for cell survival and an attractive target for antibacterial and anticancer drug development. The number of a divalent metal required for catalysis is under intense debate. E. coli MetAP was shown to be fully active with one equivalent of metal by graphical analysis, but it was inferred to require at least two metals by a Hill equation model. Herein, we report a mathematical model and detailed analysis of the stoichiometric activation of MetAP by metal cofactors. Results. Because of diverging results with significant implications in drug discovery, the experimental titration curve for Co 2+ activating MetAP was analyzed by fitting with a multiple independent binding sites (MIBS) model, and the quality of the fitting was compared to that of the Hill equation. The fitting by the MIBS model was clearly superior and indicated that complete activity is observed at a one metal to one protein ratio. The shape of the titration curve was also examined for activation of metalloenzymes in general by one or two metals. Conclusions. Considering different scenarios of MetAP activation by one or two metal ions, it is concluded that E. coli MetAP is fully active as a monometalated enzyme. Our approach can be of value in proper determination of the number of cations needed for catalysis by metalloenzymes.

Original languageEnglish
Article number32
JournalBMC Biochemistry
Volume10
Issue number1
DOIs
StatePublished - 2009

Fingerprint

Aminopeptidases
Methionine
Metals
Chemical activation
Titration
Escherichia coli
Catalysis
Binding Sites
Activation Analysis
Enzymes
Drug Discovery
Metal ions
Cations
Cells
Cell Survival
Mathematical models
Theoretical Models
Ions
Pharmaceutical Preparations
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Analysis of the stoichiometric metal activation of methionine aminopeptidase. / Chai, Sergio C.; Ye, Qizhuang.

In: BMC Biochemistry, Vol. 10, No. 1, 32, 2009.

Research output: Contribution to journalArticle

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