Disease relevance of map

• Crystals of methionine aminopeptidase from Escherichia coli have been obtained [1].
• The two authentic methionine aminopeptidase genes are differentially expressed in Bacillus subtilis [2].

High impact information on map

• Methionine aminopeptidase (MetAP) removes the amino-terminal methionine residue from newly synthesized proteins, and it is a target for the development of antibacterial and anticancer agents [3].
• The C-terminal catalytic domain is also similar to the single-domain enzyme methionine aminopeptidase that has a dinuclear cobalt center [4].
• We have performed a computational study of different protomeric states of the methionine aminopeptidase active site using a combined quantum-mechanical/molecular mechanical simulation approach [5].
• In eukaryotes, two isozymes (I and II) of methionine aminopeptidase (MetAP) catalyze the removal of the initiator methionine if the penultimate residue has a small radius of gyration (glycine, alanine, serine, threonine, proline, valine, and cysteine) [6].
• Methionine aminopeptidase (MAP), which catalyzes the removal of NH2-terminal methionine from proteins, was isolated from Saccharomyces cerevisiae [7].

Chemical compound and disease context of map

• Insertion of a methionine in front of the HIV protease cleavage site in the recombinant protein enabled synthesis of both subunits with the natural amino-terminal proline, since E. coli methionine aminopeptidase cleaves a Met-Pro amino-terminal linkage [8].
• We report the discovery of thiabendazole as a potent inhibitor (K(i) = 0.4 microM) of Escherichia coli methionine aminopeptidase (ecMetAP) and the synthesis and pharmacological evaluation of thiabendazole congeners with activity in the upper nanomolar range [9].
• Overexpression in E. coli of several proteins containing cysteine as the second amino acid residue yielded products in which the initiating methionine residue had been completely cleaved by endogenous methionine aminopeptidase [10].
• EPR spectra were recorded for methionine aminopeptidase from Escherichia coli (EcMetAP-I) samples (approximately 2.5 mM) to which one and two equivalents of Mn(II) were added (the latter is referred to as [MnMn(EcMetAP-I)]) [11].
• Escherichia coli methionine aminopeptidase with Tyr168 to alanine substitution can improve the N-terminal processing of recombinant proteins with valine at the penultimate position [12].

Biological context of map

• APPro shares a similar fold, substrate specificity, and catalytic mechanism with methionine aminopeptidase and prolidase [13].
• Metal-mediated inhibition of Escherichia coli methionine aminopeptidase: structure-activity relationships and development of a novel scoring function for metal-ligand interactions [9].
• Methionine aminopeptidase (MetAP) carries out an essential posttranslational modification of nascent proteins by removing the initiator methionine and is recognized as a potential target for developing antibacterial, antifungal, and anticancer agents [14].
• Thus, methionine aminopeptidase is essential for cell growth [15].
• We localized the methionine aminopeptidase (map) gene on the Escherichia coli chromosome next to the rpsB gene at min 4 [15].

Anatomical context of map

• A gene for a methionine aminopeptidase (MAP; EC 3.4.11.18), which catalyzes the removal of amino-terminal methionine from the growing peptide chain on the ribosome, has been cloned from the hyperthermophilic Archaeon, Pyrococcus furiosus, by a novel method effectively using its cosmid protein library, sequenced and expressed in Escherichia coli [16].

Associations of map with chemical compounds

• Sequence, structural, and kinetic analyses reveal that His350, conserved in APPro and prolidase but not in methionine aminopeptidase, forms part of a hydrophobic binding pocket that gives APPro its proline specificity [13].
• Quinolinyl sulfonamides, such as N-(quinolin-8-yl)methanesulfonamide (10) and N-(5-chloroquinolin-8-yl)methanesulfonamide (11), were identified as potent methionine aminopeptidase (MetAP) inhibitors by high throughput screening of a diverse chemical library of small organic compounds [17].
• Understanding the selectivity of fumagillin for the methionine aminopeptidase type II [18].
• Replacement of an Asn residue penultimate to the initiator Met with Ser or Gly permitted removal of the initiator Met by the endogenous methionine aminopeptidase [19].
• The formylmethionine should be removed by the combined action of a cellular deformylase and methionine aminopeptidase [20].

Analytical, diagnostic and therapeutic context of map

• Crystallization of methionine aminopeptidase from Escherichia coli [1].
• In an effort to differentiate between alternative mechanistic schemes that have been postulated for Escherichia coli methionine aminopeptidase (eMetAP), the modes of binding of a series of products and phosphorus-based transition-state analogues were determined by X-ray crystallography [21].
• Methionine aminopeptidase from the hyperthermophilic Archaeon Pyrococcus furiosus: molecular cloning and overexpression in Escherichia coli of the gene, and characteristics of the enzyme [16].
• Type I methionine aminopeptidase from Saccharomyces cerevisiae is a potential target for antifungal drug screening [22].

References