1Q7L: Zn-binding Domain Of The T347g Mutant Of Human Aminoacylase- I

Citation:
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.
PDB ID: 1Q7LDownload
MMDB ID: 26128
PDB Deposition Date: 2003/8/19
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 1.4  Å
Source Organism:
Similar Structures:
Biological Unit for 1Q7L: dimeric; determined by author and by software (PISA)
Molecular Components in 1Q7L
Label Count Molecule
Proteins (2 molecules)
1
Aminoacylase-1(Gene symbol: ACY1)
Molecule annotation
1
Aminoacylase-1(Gene symbol: ACY1)
Molecule annotation
Chemicals (3 molecules)
1
2
2
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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