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Three‐Dimensional structure of schistosoma japonicum glutathione s ‐transferase fused with a six‐amino acid conserved neutralizing epitope of gp41 from hiv
Author(s) -
Lim Kap,
Ho Joseph X.,
Keeling Kim,
Gilliland Gary L.,
Ji Xinhua,
Rüker Florian,
Carter Daniel C.
Publication year - 1994
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.5560031209
Subject(s) - molecular replacement , dimer , glutathione s transferase , stereochemistry , schistosoma japonicum , peptide sequence , protein structure , chemistry , multiple isomorphous replacement , biology , epitope , amino acid , microbiology and biotechnology , crystallography , biochemistry , glutathione , gene , enzyme , genetics , antibody , zoology , organic chemistry , helminths , schistosomiasis
The 3‐dimensional crystal structure of glutathione S ‐transferase (GST) of Schistosoma japonicum (Sj) fused with a conserved neutralizing epitope on gp41 (glycoprotein, 41 kDa) of human immunodeficiency virus type 1 (HIV‐1) (Muster T et al., 1993, J Virol 67 :6642–6647) was determined at 2.5 Å resolution. The structure of the 3‐3 isozyme rat GST of the μ gene class (Ji X, Zhang P, Armstrong RN, Gilliland GL, 1992, Biochemistry 31 :10169–10184) was used as a molecular replacement model. The structure consists of a 4‐stranded β‐sheet and 3 α‐helices in domain 1 and 5 α‐helices in domain 2. The space group of the Sj GST crystal is P4 3 2 1 2, with unit cell dimensions of a = b = 94.7 Å, and c = 58.1 Å. The crystal has 1 GST monomer per asymmetric unit, and 2 monomers that form an active dimer are related by crystallographic 2‐fold symmetry. In the binding site, the ordered structure of reduced glutathione is observed. The gp41 peptide (Glu‐Leu‐Asp‐Lys‐Trp‐Ala) fused to the C‐terminus of Sj GST forms a loop stabilized by symmetry‐related GSTs. The Sj GST structure is compared with previously determined GST structures of mammalian gene classes μ, α, and π. Conserved amino acid residues among the 4 GSTs that are important for hydrophobic and hydrophilic interactions for dimer association and glutathione binding are discussed.