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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]] 1.40&Aring;' scene=''>
<StructureSection load='1q7l' size='340' side='right'caption='[[1q7l]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1q7l]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q7L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1Q7L FirstGlance]. <br>
<table><tr><td colspan='2'>[[1q7l]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q7L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Q7L FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GLY:GLYCINE'>GLY</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.4&#8491;</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLY:GLYCINE'>GLY</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=1q7l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q7l OCA], [https://pdbe.org/1q7l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1q7l RCSB], [https://www.ebi.ac.uk/pdbsum/1q7l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1q7l ProSAT]</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>
</table>
</table>
== Disease ==
== Disease ==
[[http://www.uniprot.org/uniprot/ACY1_HUMAN ACY1_HUMAN]] Defects in ACY1 are the cause of aminoacylase-1 deficiency (ACY1D) [MIM:[http://omim.org/entry/609924 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.<ref>PMID:16465618</ref> <ref>PMID:16274666</ref> <ref>PMID:17562838</ref> <ref>PMID:21414403</ref>
[https://www.uniprot.org/uniprot/ACY1_HUMAN ACY1_HUMAN] Defects in ACY1 are the cause of aminoacylase-1 deficiency (ACY1D) [MIM:[https://omim.org/entry/609924 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.<ref>PMID:16465618</ref> <ref>PMID:16274666</ref> <ref>PMID:17562838</ref> <ref>PMID:21414403</ref>  
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/ACY1_HUMAN ACY1_HUMAN]] Involved in the hydrolysis of N-acylated or N-acetylated amino acids (except L-aspartate).<ref>PMID:12933810</ref>
[https://www.uniprot.org/uniprot/ACY1_HUMAN ACY1_HUMAN] Involved in the hydrolysis of N-acylated or N-acetylated amino acids (except L-aspartate).<ref>PMID:12933810</ref>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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>
   </jmolCheckbox>
   </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1q7l ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.
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<ref>PMID:12933810</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
==See Also==
</div>
*[[Aminoacylase 3D structures|Aminoacylase 3D structures]]
<div class="pdbe-citations 1q7l" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: N-acyl-aliphatic-L-amino acid amidohydrolase]]
[[Category: Large Structures]]
[[Category: Alary, A]]
[[Category: Alary A]]
[[Category: Cygler, M]]
[[Category: Cygler M]]
[[Category: Hecker, R]]
[[Category: Hecker R]]
[[Category: Lindner, H A]]
[[Category: Lindner HA]]
[[Category: Lunin, V V]]
[[Category: Lunin VV]]
[[Category: Menard, R]]
[[Category: Menard R]]
[[Category: Aminoacylase-1]]
[[Category: Catalysis]]
[[Category: Enzyme dimerization]]
[[Category: Hydrolase]]
[[Category: Site-directed mutagenesis]]
[[Category: Structure comparison]]

Latest revision as of 11:13, 14 February 2024

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

Structural highlights

1q7l is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.4Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

See Also

References

  1. ↑ Sass JO, Mohr V, Olbrich H, Engelke U, Horvath J, Fliegauf M, Loges NT, Schweitzer-Krantz S, Moebus R, Weiler P, Kispert A, Superti-Furga A, Wevers RA, Omran H. Mutations in ACY1, the gene encoding aminoacylase 1, cause a novel inborn error of metabolism. Am J Hum Genet. 2006 Mar;78(3):401-9. Epub 2006 Jan 18. PMID:16465618 doi:S0002-9297(07)62380-5
  2. ↑ Van Coster RN, Gerlo EA, Giardina TG, Engelke UF, Smet JE, De Praeter CM, Meersschaut VA, De Meirleir LJ, Seneca SH, Devreese B, Leroy JG, Herga S, Perrier JP, Wevers RA, Lissens W. Aminoacylase I deficiency: a novel inborn error of metabolism. Biochem Biophys Res Commun. 2005 Dec 23;338(3):1322-6. Epub 2005 Nov 2. PMID:16274666 doi:S0006-291X(05)02421-6
  3. ↑ Sass JO, Olbrich H, Mohr V, Hart C, Woldseth B, Krywawych S, Bjurulf B, Lakhani PK, Buchdahl RM, Omran H. Neurological findings in aminoacylase 1 deficiency. Neurology. 2007 Jun 12;68(24):2151-3. PMID:17562838 doi:10.1212/01.wnl.0000264933.56204.e8
  4. ↑ Sommer A, Christensen E, Schwenger S, Seul R, Haas D, Olbrich H, Omran H, Sass JO. The molecular basis of aminoacylase 1 deficiency. Biochim Biophys Acta. 2011 Jun;1812(6):685-90. doi: 10.1016/j.bbadis.2011.03.005., Epub 2011 Mar 23. PMID:21414403 doi:10.1016/j.bbadis.2011.03.005
  5. ↑ Lindner HA, Lunin VV, Alary A, Hecker R, Cygler M, Menard R. Essential roles of zinc ligation and enzyme dimerization for catalysis in the aminoacylase-1/M20 family. J Biol Chem. 2003 Nov 7;278(45):44496-504. Epub 2003 Aug 21. PMID:12933810 doi:http://dx.doi.org/10.1074/jbc.M304233200

1q7l, resolution 1.40Å

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