1q7l: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1q7l.gif|left|200px]] | [[Image:1q7l.gif|left|200px]] | ||
<!-- | |||
The line below this paragraph, containing "STRUCTURE_1q7l", creates the "Structure Box" on the page. | |||
You may change the PDB parameter (which sets the PDB file loaded into the applet) | |||
or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |||
or leave the SCENE parameter empty for the default display. | |||
| | --> | ||
| | {{STRUCTURE_1q7l| PDB=1q7l | SCENE= }} | ||
}} | |||
'''Zn-binding domain of the T347G mutant of human aminoacylase-I''' | '''Zn-binding domain of the T347G mutant of human aminoacylase-I''' | ||
| Line 35: | Line 32: | ||
[[Category: Lunin, V V.]] | [[Category: Lunin, V V.]] | ||
[[Category: Menard, R.]] | [[Category: Menard, R.]] | ||
[[Category: | [[Category: Aminoacylase-1]] | ||
[[Category: | [[Category: Catalysis]] | ||
[[Category: | [[Category: Enzyme dimerization]] | ||
[[Category: | [[Category: Site-directed mutagenesis]] | ||
[[Category: | [[Category: Structure comparison]] | ||
[[Category: | [[Category: Zinc]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 05:58:09 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 05:58, 3 May 2008
Zn-binding domain of the T347G mutant of human aminoacylase-I
OverviewOverview
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.
DiseaseDisease
Known disease associated with this structure: Aminoacylase 1 deficiency OMIM:[104620]
About this StructureAbout this Structure
1Q7L is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
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 Sat May 3 05:58:09 2008