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PDBsum entry 1f3b
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Residue r216 and catalytic efficiency of a murine class alpha glutathione s-Transferase toward benzo[a]pyrene 7(r),8(s)-Diol 9(s), 10(r)-Epoxide.
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Authors
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Y.Gu,
S.V.Singh,
X.Ji.
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Ref.
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Biochemistry, 2000,
39,
12552-12557.
[DOI no: ]
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PubMed id
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Abstract
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Murine class alpha glutathione S-transferase A1-1 (mGSTA1-1), unlike mammalian
class alpha GSTs, is the most efficient in the 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] [Hu, X., Srivastava, S. K., Xia, H., Awasthi, Y. C., and Singh,
S. V. (1996) J. Biol. Chem. 271, 32684-32688]. Here, we report the crystal
structures of mGSTA1-1 in complex with GSH and with the GSH conjugate of
(+)-anti-BPDE (GSBpd) at 1.9 and 2.0 A resolution, respectively. Both crystals
belong to monoclinic space group C2 with one dimer in the asymmetric unit. The
structures reveal that, within one subunit, the GSH moiety interacts with
residues Y8, R14, K44, Q53, V54, Q66, and T67, whereas the hydrophobic moiety of
GSBpd interacts with the side chains of F9, R14, M207, A215, R216, F219, and
I221. In addition, the GSH moiety interacts with D100 and R130 from the other
subunit across the dimer interface. The structural comparison between
mGSTA1-1.GSH and mGSTA1-1.GSBpd reveals significant conformational differences.
The movement of helix alpha9 brings the residues on the helix into direct
interaction with the product. Most noticeable are the positional displacement
and conformational change of R216, one of the residues located in helix alpha9.
The side chain of R216, which points away from the H-site in the mGSTA1-1.GSH
complex, probes into the active site and becomes parallel with the aromatic ring
system of GSBpd. Moreover, the guanidinium group of R216 shifts approximately 8
A and forms a strong hydrogen bond with the C8 hydroxyl group of GSBpd,
suggesting that the electrostatic assistance provided by the guanidinium group
facilitates the ring-opening reaction of (+)-anti-BPDE. The structure of
mGSTA1-1. GSBpd is also compared with those of hGSTP1-1[V104,A113].GSBpd,
hGSPA1-1.S-benzylglutathione, and mGSTA4-4.
4-S-glutathionyl-5-pentyltetrahydrofuran-2-ol. The comparison provides further
evidence that supports the functional roles of R216 and helix alpha9. The lack
of mobility of helix alpha9 and/or the lack of electrostatic assistance from
R216 may be responsible for the relatively lower activity of hGSTA1-1, mGSTA4-4,
and hGSTP1-1 toward (+)-anti-BPDE.
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Secondary reference #1
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Title
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Crystal structure of a murine glutathione s-Transferase in complex with a glutathione conjugate of 4-Hydroxynon-2-Enal in one subunit and glutathione in the other: evidence of signaling across the dimer interface.
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Authors
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B.Xiao,
S.P.Singh,
B.Nanduri,
Y.C.Awasthi,
P.Zimniak,
X.Ji.
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Ref.
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Biochemistry, 1999,
38,
11887-11894.
[DOI no: ]
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PubMed id
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