1q7l

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{{STRUCTURE_1q7l| PDB=1q7l | SCENE= }}
{{STRUCTURE_1q7l| PDB=1q7l | SCENE= }}
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'''Zn-binding domain of the T347G mutant of human aminoacylase-I'''
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===Zn-binding domain of the T347G mutant of human aminoacylase-I===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_12933810}}
==Disease==
==Disease==
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[[Category: Structure comparison]]
[[Category: Structure comparison]]
[[Category: Zinc]]
[[Category: Zinc]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 05:58:09 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 14:34:29 2008''

Revision as of 11:34, 28 July 2008

Image:1q7l.png

Template:STRUCTURE 1q7l

Contents

Zn-binding domain of the T347G mutant of human aminoacylase-I

Template:ABSTRACT PUBMED 12933810

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. 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

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