Specificity for inhibitors of metal-substituted methionine aminopeptidase

Jing Ya Li, Ling Ling Chen, Yong Mei Cui, Qun Li Luo, Jia Li, Fa Jun Nan, Qizhuang Ye

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Methionine aminopeptidases (MetAPs) have been studied in vitro as Co(II) enzymes, but their in vivo metal remains to be defined. While activation of Escherichia coli MetAP (EcMetAP1) by Co(II), Mn(II), and Zn(II) was detectable by a colorimetric Met-S-Gly-Phe assay, significant activation by Ni(II) was shown in a fluorescence Met-AMC assay, in addition to Co(II) and Mn(II) activation. When tested on the metal-substituted EcMetAP1s, a few inhibitors that we obtained recently from a random screening on Co-EcMetAP1 either became much weak or lost activity on Mn- or Zn-EcMetAP1, although they kept inhibitory activity on Ni-EcMetAP1. A couple of peptidic inhibitors and the methionine mimetic (3R)-amino-(2S)-hydroxyheptanoic acid (AHHpA, 6) maintained moderate activities on Co-, Mn-, Zn-, and Ni-EcMetAP1s. Our results clearly demonstrate that the metal-substitution has changed the enzyme specificity for substrates and inhibitors. Therapeutic applications call for inhibitors specific for MetAP with a physiologically relevant metal at its active site.

Original languageEnglish (US)
Pages (from-to)172-179
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume307
Issue number1
DOIs
StatePublished - Jul 18 2003
Externally publishedYes

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Aminopeptidases
Methionine
Metals
Chemical activation
Assays
glycylphenylalanine
Enzymes
Substrate Specificity
Escherichia coli
Catalytic Domain
Screening
Substitution reactions
Fluorescence
Acids
Substrates
Therapeutics

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Specificity for inhibitors of metal-substituted methionine aminopeptidase. / Li, Jing Ya; Chen, Ling Ling; Cui, Yong Mei; Luo, Qun Li; Li, Jia; Nan, Fa Jun; Ye, Qizhuang.

In: Biochemical and Biophysical Research Communications, Vol. 307, No. 1, 18.07.2003, p. 172-179.

Research output: Contribution to journalArticle

Li, Jing Ya ; Chen, Ling Ling ; Cui, Yong Mei ; Luo, Qun Li ; Li, Jia ; Nan, Fa Jun ; Ye, Qizhuang. / Specificity for inhibitors of metal-substituted methionine aminopeptidase. In: Biochemical and Biophysical Research Communications. 2003 ; Vol. 307, No. 1. pp. 172-179.
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