1q7l: Difference between revisions
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==Zn-binding domain of the T347G mutant of human aminoacylase-I== | ==Zn-binding domain of the T347G mutant of human aminoacylase-I== | ||
<StructureSection load='1q7l' size='340' side='right' caption='[[1q7l]], [[Resolution|resolution]] 1.40Å' scene=''> | <StructureSection load='1q7l' size='340' side='right' caption='[[1q7l]], [[Resolution|resolution]] 1.40Å' scene=''> | ||
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ACY1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ACY1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/N-acyl-aliphatic-L-amino_acid_amidohydrolase N-acyl-aliphatic-L-amino acid amidohydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.14 3.5.1.14] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/N-acyl-aliphatic-L-amino_acid_amidohydrolase N-acyl-aliphatic-L-amino acid amidohydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.14 3.5.1.14] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1q7l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q7l OCA], [http://pdbe.org/1q7l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1q7l RCSB], [http://www.ebi.ac.uk/pdbsum/1q7l PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1q7l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q7l OCA], [http://pdbe.org/1q7l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1q7l RCSB], [http://www.ebi.ac.uk/pdbsum/1q7l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1q7l ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
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Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/q7/1q7l_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/q7/1q7l_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
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[[Category: Site-directed mutagenesis]] | [[Category: Site-directed mutagenesis]] | ||
[[Category: Structure comparison]] | [[Category: Structure comparison]] | ||
[[Category: Zinc]] | |||
Revision as of 11:06, 24 February 2018
Zn-binding domain of the T347G mutant of human aminoacylase-IZn-binding domain of the T347G mutant of human aminoacylase-I
Structural highlights
Disease[ACY1_HUMAN] Defects in ACY1 are the cause of aminoacylase-1 deficiency (ACY1D) [MIM:609924]. ACY1D results in a metabolic disorder manifesting with encephalopathy, unspecific psychomotor delay, psychomotor delay with atrophy of the vermis and syringomyelia, marked muscular hypotonia or normal clinical features. Epileptic seizures are a frequent feature. All affected individuals exhibit markedly increased urinary excretion of several N-acetylated amino acids.[1] [2] [3] [4] Function[ACY1_HUMAN] Involved in the hydrolysis of N-acylated or N-acetylated amino acids (except L-aspartate).[5] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedMembers 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. 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[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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