Aspartoacylase

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 10: Line 10:
==About this Structure==
==About this Structure==
-
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 <scene name='49/498146/Cv/2'>catalytic site of aspartoacylase</scene> 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.<ref name="Abstract"> PMID: 17194761</ref>.
+
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.<ref name="Abstract"> PMID: 17194761</ref>.
-
2GU2 is a 2 chains structure of sequences from [http://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].
+
2GU2 is a 2 chains structure of sequences from [http://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].
-
 
+
 +
<scene name='49/498146/Cv/2'>Catalytic site</scene> of human aspartocyclase with aspartate analogue and Zn+2.
</StructureSection>
</StructureSection>
==GO Annotation==
==GO Annotation==

Revision as of 10:10, 15 November 2015

Human aspartocyclase dimer complex with aspartate analogue and Zn+2 (grey) 2o4h

Drag the structure with the mouse to rotate

Contents

GO Annotation

Database ID Symbol Qualifier GO Identifier GO Term Name Aspect Evidence Reference With Taxon Date Assigned By Product Form ID
Process
UniProtKB Q9R1T5 Aspa GO:0008152 metabolic process P IEA InterPro2GO InterPro:IPR007036 10116 20101127 InterPro
UniProtKB Q9R1T5 Aspa GO:0022010 central nervous system myelination P IEP PMID:12524181 10116 20070129 RGD
UniProtKB Q9R1T5 Aspa GO:0048714 positive regulation of oligodendrocyte differentiation P IMP PMID:16634055 10116 20070129 RGD
Function
UniProtKB Q9R1T5 Aspa GO:0016787 hydrolase activity F IEA Swiss-Prot Keywords2GO SP_KW:KW-0378 10116 20101127 UniProtKB
UniProtKB Q9R1T5 Aspa GO:0016788 hydrolase activity, acting on ester bonds F IEA InterPro2GO InterPro:IPR007036 10116 20101127 InterPro
UniProtKB Q9R1T5 Aspa GO:0019807 aspartoacylase activity F IEA EC2GO EC:3.5.1.15 10116 20100703 UniProtKB
UniProtKB Q9R1T5 Aspa GO:0019807 aspartoacylase activity F TAS PMID:12524181 10116 20050217 RGD
UniProtKB Q9R1T5 Aspa GO:0046872 metal ion binding F IEA Swiss-Prot Keywords2GO SP_KW:KW-0479 10116 20101127 UniProtKB
Component
UniProtKB Q9R1T5 Aspa GO:0005634 nucleus C IDA PMID:16935940 10116 20070129 RGD
UniProtKB Q9R1T5 Aspa GO:0005634 nucleus C IEA Swiss-Prot Keywords2GO SP_KW:KW-0539 10116 20101127 UnitProtKB
UniProtKB Q9R1T5 Aspa GO:0005634 nucleus C IEA Subcellular Location2GO SP_SL:SL-0191 10116 20101127 UniProtKB
UniProtKB Q9R1T5 Aspa GO:0005737 cytoplasm C IDA PMID:16935940 10116 20070129 RGD
UniProtKB Q9R1T5 Aspa GO:0005737 cytoplasm C IEA Swiss-Prot Keywords2GO SP_KW:KW-0963 10116 20101127 UniProtKB
UniProtKB Q9R1T5 Aspa GO:0005737 cytoplasm C IEA Subcellular Location2GO SP_SL:SL-0086 10116 20101127 UniProtKB
[3]

3D structures of aspartoacylase

Updated on 15-November-2015

2gu2, 2q4z – AAC – rat
2i3c, 2q51, 2o53 – hAAC – human
2o4h – hAAC + intermediate analog
4mri, 4mxu, 4nfr, 4tnu - hAAC (mutant) + intermediate analog
3nfz – mAAC-2 (mutant) + acetyl-tyrosine – mouse
3nh4 – mAAC-2
3nh5 - mAAC-2 (mutant)
3nh8 - mAAC-2 (mutant) + acetyl-dichlorovinyl-cysteine


References

  1. ↑ http://www.uniprot.org/uniprot/Q9R1T5
  2. ↑ Bitto E, Bingman CA, Wesenberg GE, McCoy JG, Phillips GN Jr. Structure of aspartoacylase, the brain enzyme impaired in Canavan disease. Proc Natl Acad Sci U S A. 2007 Jan 9;104(2):456-61. Epub 2006 Dec 28. PMID:17194761
  3. ↑ http://www.ebi.ac.uk/QuickGO/GProtein?ac=Q9R1T5

Additional Literature and Resources

  • Bitto E, Bingman CA, Wesenberg GE, McCoy JG, Phillips GN Jr. Structure of aspartoacylase, the brain enzyme impaired in Canavan disease. Proc Natl Acad Sci U S A. 2007 Jan 9;104(2):456-61. Epub 2006 Dec 28. PMID:17194761

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky

Retrieved from "http://52.214.119.220/wiki/index.php/Aspartoacylase"
Personal tools