1ML6

Crystal Structure of mGSTA2-2 in Complex with the Glutathione Conjugate of Benzo[a]pyrene-7(R),8(S)-Diol-9(S),10(R)-Epoxide

Summary for 1ML6

• Entry DOI: 10.2210/pdb1ml6/pdb
• Related: 1F3A 1F3B
• Descriptor: Glutathione S-Transferase GT41A, 2-AMINO-4-[1-(CARBOXYMETHYL-CARBAMOYL)-2-(9-HYDROXY-7,8-DIOXO-7,8,9,10-TETRAHYDRO-BENZO[DEF]CHRYSEN-10-YLSULFANYL)-ETHYLCARBAMOYL]-BUTYRIC ACID, ISOPROPYL ALCOHOL, ... (4 entities in total)
• Functional Keywords: gst detoxification, mgsta2-2, transferase
• Biological source: Mus musculus (house mouse)
• Total number of polymer chains: 2
• Total formula weight: 52243.02

Authors

Gu, Y.,Xiao, B.,Wargo, H.L.,Bucher, M.H.,Singh, S.V.,Ji, X. (deposition date: 2002-08-30, release date: 2003-04-15, Last modification date: 2024-11-20)

Primary citation

Gu, Y.,Xiao, B.,Wargo, H.L.,Bucher, M.H.,Singh, S.V.,Ji, X.
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
Biochemistry, 42:917-921, 2003

PubMed 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.

PubMed: 12549910
DOI: 10.1021/bi026778+

Experimental method

X-RAY DIFFRACTION (1.9 Å)