2gu2: Difference between revisions
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< | ==Crystal Structure of an Aspartoacylase from Rattus norvegicus== | ||
<StructureSection load='2gu2' size='340' side='right'caption='[[2gu2]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2gu2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GU2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GU2 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.805Å</td></tr> | |||
-- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=2gu2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gu2 OCA], [https://pdbe.org/2gu2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gu2 RCSB], [https://www.ebi.ac.uk/pdbsum/2gu2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gu2 ProSAT], [https://www.topsan.org/Proteins/CESG/2gu2 TOPSAN]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ACY2_RAT ACY2_RAT] Catalyzes the deacetylation of N-acetylaspartic acid (NAA) to produce acetate and L-aspartate. NAA occurs in high concentration in brain and its hydrolysis NAA plays a significant part in the maintenance of intact white matter (By similarity). | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gu/2gu2_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</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/main_output.php?pdb_ID=2gu2 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Aspartoacylase catalyzes hydrolysis of N-acetyl-l-aspartate to aspartate and acetate in the vertebrate brain. Deficiency in this activity leads to spongiform degeneration of the white matter of the brain and is the established cause of Canavan disease, a fatal progressive leukodystrophy affecting young children. We present crystal structures of recombinant human and rat aspartoacylase refined to 2.8- and 1.8-A resolution, respectively. The structures revealed that the N-terminal domain of aspartoacylase adopts a protein fold similar to that of zinc-dependent hydrolases related to carboxypeptidases A. The catalytic site of aspartoacylase shows close structural similarity to those of carboxypeptidases despite only 10-13% sequence identity between these proteins. About 100 C-terminal residues of aspartoacylase form a globular domain with a two-stranded beta-sheet linker that wraps around the N-terminal domain. The long channel leading to the active site is formed by the interface of the N- and C-terminal domains. The C-terminal domain is positioned in a way that prevents productive binding of polypeptides in the active site. The structures revealed that residues 158-164 may undergo a conformational change that results in opening and partial closing of the channel entrance. We hypothesize that the catalytic mechanism of aspartoacylase is closely analogous to that of carboxypeptidases. We identify residues involved in zinc coordination, and propose which residues may be involved in substrate binding and catalysis. The structures also provide a structural framework necessary for understanding the deleterious effects of many missense mutations of human aspartoacylase. | |||
Structure of aspartoacylase, the brain enzyme impaired in Canavan disease.,Bitto E, Bingman CA, Wesenberg GE, McCoy JG, Phillips GN Jr Proc Natl Acad Sci U S A. 2007 Jan 9;104(2):456-61. Epub 2006 Dec 28. PMID:17194761<ref>PMID:17194761</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2gu2" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Aminoacylase 3D structures|Aminoacylase 3D structures]] | |||
*[[Aspartoacylase 3D structures|Aspartoacylase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
== | </StructureSection> | ||
[[ | [[Category: Large Structures]] | ||
== | |||
< | |||
[[Category: | |||
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
[[Category: Bingman | [[Category: Bingman CA]] | ||
[[Category: Bitto | [[Category: Bitto E]] | ||
[[Category: Phillips Jr GN]] | |||
[[Category: Phillips | [[Category: Wesenberg GE]] | ||
[[Category: Wesenberg | |||
Latest revision as of 03:59, 21 November 2024
Crystal Structure of an Aspartoacylase from Rattus norvegicusCrystal Structure of an Aspartoacylase from Rattus norvegicus
Structural highlights
FunctionACY2_RAT Catalyzes the deacetylation of N-acetylaspartic acid (NAA) to produce acetate and L-aspartate. NAA occurs in high concentration in brain and its hydrolysis NAA plays a significant part in the maintenance of intact white matter (By similarity). 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 PubMedAspartoacylase catalyzes hydrolysis of N-acetyl-l-aspartate to aspartate and acetate in the vertebrate brain. Deficiency in this activity leads to spongiform degeneration of the white matter of the brain and is the established cause of Canavan disease, a fatal progressive leukodystrophy affecting young children. We present crystal structures of recombinant human and rat aspartoacylase refined to 2.8- and 1.8-A resolution, respectively. The structures revealed that the N-terminal domain of aspartoacylase adopts a protein fold similar to that of zinc-dependent hydrolases related to carboxypeptidases A. The catalytic site of aspartoacylase shows close structural similarity to those of carboxypeptidases despite only 10-13% sequence identity between these proteins. About 100 C-terminal residues of aspartoacylase form a globular domain with a two-stranded beta-sheet linker that wraps around the N-terminal domain. The long channel leading to the active site is formed by the interface of the N- and C-terminal domains. The C-terminal domain is positioned in a way that prevents productive binding of polypeptides in the active site. The structures revealed that residues 158-164 may undergo a conformational change that results in opening and partial closing of the channel entrance. We hypothesize that the catalytic mechanism of aspartoacylase is closely analogous to that of carboxypeptidases. We identify residues involved in zinc coordination, and propose which residues may be involved in substrate binding and catalysis. The structures also provide a structural framework necessary for understanding the deleterious effects of many missense mutations of human aspartoacylase. Structure of aspartoacylase, the brain enzyme impaired in Canavan disease.,Bitto E, Bingman CA, Wesenberg GE, McCoy JG, Phillips GN Jr Proc Natl Acad Sci U S A. 2007 Jan 9;104(2):456-61. Epub 2006 Dec 28. PMID:17194761[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
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