1Q7L
Zn-binding domain of the T347G mutant of human aminoacylase-I
Summary for 1Q7L
Entry DOI | 10.2210/pdb1q7l/pdb |
Descriptor | Aminoacylase-1, ZINC ION, GLYCINE, ... (5 entities in total) |
Functional Keywords | aminoacylase-1, catalysis, enzyme dimerization, site-directed mutagenesis, structure comparison, zinc, hydrolase |
Biological source | Homo sapiens (human) More |
Cellular location | Cytoplasm: Q03154 Q03154 |
Total number of polymer chains | 4 |
Total formula weight | 65109.28 |
Authors | Lindner, H.A.,Lunin, V.V.,Alary, A.,Hecker, R.,Cygler, M.,Menard, R. (deposition date: 2003-08-19, release date: 2004-01-20, Last modification date: 2024-02-14) |
Primary citation | Lindner, H.A.,Lunin, V.V.,Alary, A.,Hecker, R.,Cygler, M.,Menard, R. Essential roles of zinc ligation and enzyme dimerization for catalysis in the aminoacylase-1/M20 family. J.Biol.Chem., 278:44496-44504, 2003 Cited by PubMed Abstract: Members of the aminoacylase-1 (Acy1)/M20 family of aminoacylases and exopeptidases exist as either monomers or homodimers. They contain a zinc-binding domain and a second domain mediating dimerization in the latter case. The roles that both domains play in catalysis have been investigated for human Acy1 (hAcy1) by x-ray crystallography and by site-directed mutagenesis. Structure comparison of the dinuclear zinc center in a mutant of hAcy1 reported here with dizinc centers in related enzymes points to a difference in zinc ligation in the Acy1/M20 family. Mutational analysis supports catalytic roles of zinc ions, a vicinal glutamate, and a histidine from the dimerization domain. By complementing different active site mutants of hAcy1, we show that catalysis occurs at the dimer interface. Reinterpretation of the structure of a monomeric homolog, peptidase V, reveals that a domain insertion mimics dimerization. We conclude that monomeric and dimeric Acy1/M20 family members share a unique active site architecture involving both enzyme domains. The study may provide means to improve homologous carboxypeptidase G2 toward application in antibody-directed enzyme prodrug therapy. PubMed: 12933810DOI: 10.1074/jbc.M304233200 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (1.4 Å) |
Structure validation
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