Design and synthesis of chromogenic thiopeptolide substrates as MetAPs active site probes.
Twenty one chromogenic thiopeptolide substrates were designed and synthesized as the active site probes and analyzed with each S1 site of mutant residues and enzymes of wild-type MetAP1s. The preliminary enzymatic experiments indicate that cysteine 70 or 202, at either Escherichia coli or human MetAP1, played a crucial role in the methionine hydrolysis.
Cui
Yong-Mei
YM
Chinese National Center for Drug Screening, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 189 Guo Shou Jing Road, ZhangJiang Hi-Tech Park, Shanghai 201203, China.
Li
Jing-Ya
JY
Chen
Ling-Ling
LL
Li
Jia
J
Ye
Qi-Zhuang
QZ
Nan
Fa-Jun
FJ
D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002863:Chromogenic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D003524:Cyclosporins / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology; D006801:Humans; D006868:Hydrolysis; D008715:Methionine / Q000378:metabolism*; D063208:Methionyl Aminopeptidases; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D017354:Point Mutation; D013438:Sulfhydryl Compounds / Q000032:analysis
D002863:Chromogenic Compounds; D003524:Cyclosporins; D009842:Oligopeptides; D013438:Sulfhydryl Compounds; D008715:Methionine; D000626:Aminopeptidases; D063208:Methionyl Aminopeptidases