1q7l
From Proteopedia
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Zn-binding domain of the T347G mutant of human aminoacylase-I
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Overview
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.
Disease
Known disease associated with this structure: Aminoacylase 1 deficiency OMIM:[104620]
About this Structure
1Q7L is a Protein complex structure of sequences from Homo sapiens with ZN and GLY as ligands. Active as Aminoacylase, with EC number 3.5.1.14 Full crystallographic information is available from OCA.
Reference
Essential roles of zinc ligation and enzyme dimerization for catalysis in the aminoacylase-1/M20 family., Lindner HA, Lunin VV, Alary A, Hecker R, Cygler M, Menard R, J Biol Chem. 2003 Nov 7;278(45):44496-504. Epub 2003 Aug 21. PMID:12933810
Page seeded by OCA on Mon Nov 12 18:51:19 2007
