title: Residues 207, 216, and 221 and the catalytic activity of mGSTA1-1 and mGSTA2-2 toward benzo[a]pyrene-(7R,8S)-diol-(9S,10R)-epoxide.
abstract: Murine class alpha glutathione S-transferase subunit types A2 (mGSTA2-2) and A1 (mGSTA1-1) have high catalytic efficiency for glutathione (GSH) conjugation of the ultimate carcinogenic metabolite of benzo[a]pyrene, (+)-anti-7,8-dihydroxy-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene, [(+)-anti-BPDE]. Only 10 residues differ between the sequences of mGSTA1-1 and 2-2. However, the catalytic efficiency of mGSTA1-1 for GSH conjugation of (+)-anti-BPDE is >3-fold higher as compared with mGSTA2-2. The crystal structure of mGSTA1-1 in complex with the GSH conjugate of (+)-anti-7,8-dihydroxy-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (GSBpd) reveals that R216 and I221 in the last helix play important roles in catalysis [Gu, Y., Singh, S. V., and Ji, X. (2000) Biochemistry 39, 12552-12557]. The crystal structure of mGSTA2-2 in complex with GSBpd has been determined, which reveals a different binding mode of GSBpd. Comparison of the two structures suggests that residues 207 and 221 are responsible for the different binding mode of GSBpd and therefore contribute to the distinct catalytic efficiency of the two isozymes.
authors.affiliation: Macromolecular Crystallographic Laboratory, National Cancer Institute, Frederick, Maryland 21702, USA.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Gu
authors.forename: Bing
authors.initials: B
authors.lastname: Xiao
authors.forename: Heather L
authors.initials: HL
authors.lastname: Wargo
authors.forename: Matthew H
authors.initials: MH
authors.lastname: Bucher
authors.forename: Shivendra V
authors.initials: SV
authors.lastname: Singh
authors.forename: Xinhua
authors.initials: X
authors.lastname: Ji
mesh_terms: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000737:chemistry* / Q000378:metabolism; D000409:Alanine / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D001120:Arginine / Q000737:chemistry; D001580:Benzopyrenes / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D018736:DNA Adducts / Q000737:chemistry* / Q000378:metabolism; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism; D005982:Glutathione Transferase / Q000737:chemistry* / Q000378:metabolism; D007527:Isoenzymes / Q000737:chemistry* / Q000378:metabolism; D007532:Isoleucine / Q000737:chemistry; D007930:Leucine / Q000737:chemistry; D008715:Methionine / Q000737:chemistry; D051379:Mice; D010649:Phenylalanine / Q000737:chemistry; D021122:Protein Subunits / Q000737:chemistry* / Q000378:metabolism; D055672:Static Electricity; D013379:Substrate Specificity
chemical_list: D000596:Amino Acids; D001580:Benzopyrenes; D018736:DNA Adducts; D007527:Isoenzymes; D021122:Protein Subunits; C121255:anti-benzo(a)pyrene-dA adduct; C113118:glutathione-BPDE conjugate; D007532:Isoleucine; D010649:Phenylalanine; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D001120:Arginine; D008715:Methionine; D005982:Glutathione Transferase; C119995:glutathione S-transferase alpha; D005978:Glutathione; D007930:Leucine; D000409:Alanine