Aspartoacylase is a hydrolyticenzyme (EC 3.5.1.15, also called aminoacylase II, ASPA and other names[a]) that in humans is encoded by the ASPAgene. ASPA catalyzes the deacylation of N-acetyl-l-aspartate (N-acetylaspartate) into aspartate and acetate.[7][8] It is a zinc-dependent hydrolase that promotes the deprotonation of water to use as a nucleophile in a mechanism analogous to many other zinc-dependent hydrolases.[9] It is most commonly found in the brain, where it controls the levels of N-acetyl-l-aspartate. Mutations that result in loss of aspartoacylase activity are associated with Canavan disease, a rare autosomal recessiveneurodegenerative disease.[10]
Aspartoacylase is a dimer of two identical monomers of 313 amino acids and uses a zinc cofactor in each.[5][11] There are two distinct domains in each monomer: the N-terminal domain from residues 1-212 and the C-terminal domain from residues 213–313.[12] The N-terminal domain of aspartoacylase is similar to that of zinc-dependent hydrolases such as carboxypeptidaseA. However, carboxypeptidases do not have something similar to the C-domain. In carboxypeptidase A, the active site is accessible to large substrates like the bulky C-terminal residue of polypeptides, whereas the C-domain sterically hinders access to the active site in aspartoacylase. Instead, the N-domain and C-domain of aspartoacylase form a deep narrow channel that leads to the active site.[5]
The zinc cofactor is found at the active site and is held by Glu-24, His-21, and His 116.[13] The substrate is held in place by Arg-63, Asn-70, Arg-71, Tyr-164, Arg-168, and Tyr-288.[5] The zinc cofactor is used to lower the pKa of a ligated water molecule so that an attack on N-acetyl-L-aspartate may occur and to stabilize the resulting tetrahedral intermediate along with Arg-63, and Glu-178.[13]
A monomer of aspartoacylase with the N-domain in green, C-domain in yellow, and zinc cofactor in red. Generated from 2I3C.[5]Active site of aspartoacylase with a bound N-phosphonamidate-L-aspartate. This is a tetrahedral intermediate analogue with phosphorus replacing the attacked carbon. In the structure, zinc, Arg-63, and Glu-178 are stabilizing the tetrahedral intermediate. Generated from 2O4H.[13]
Mechanismedit
There are two types of possible mechanisms for zinc-dependent hydrolases depending on what is the nucleophile. The first uses deprotonated water and the second attacks with an aspartate or glutamate first forming an anhydride.[14] Aspartoacylase follows the deprotonated water mechanism.[13] Zinc lowers the pKa of a ligated water molecule and the reaction proceeds via an attack on N-acetyl-l-aspartate when the water molecule is deprotonated by Glu-178.[5] This leads to a tetrahedral intermediate that is stabilized by the zinc, Arg-63, and Glu-178.[13] Finally, the carbonyl is then reformed, the bond with nitrogen is broken, and the nitrogen is protonated by the proton taken by Glu-178 all in one concerted step.[14]
Aspartoacylase mechanism.[13] All the coordinating residues are not shown for clarity.
Biological functionedit
Aspartoacylase is used to metabolize N-acetyl-L-aspartate by catalyzing its deacylation. Aspartoacylase prevents the buildup of N-acetyl-L-aspartate in the brain. It is believed that controlling N-acetyl-L-aspartate levels is essential for developing and maintaining white matter.[5] It is not known why so much N-acetyl-L-aspartate is produced in the brain nor what its primary function is.[15] However, one hypothesis is that it is potentially used as a chemical reservoir that can be tapped into for acetate for acetyl-CoA synthesis or aspartate for glutamate synthesis.[15][16] This way, N-acetyl-L-aspartate can be used to transport these precursor molecules and aspartoacylase is used to release them. For example, N-acetyl-L-aspartate produced in neurons can be transported into oligodendrocytes and the acetate released can be used for myelin synthesis.[12][17] Another hypothesis is that N-acetyl-L-aspartate is essential osmolyte that acts as a molecular water pump that helps maintain a proper fluid balance in the brain.[18]
Disease relevanceedit
Mutations that lead to loss of aspartoacylase activity have been identified as the cause of Canavan disease.[19] Canavan disease is a rare autosomal recessive disorder that causes spongy degeneration of the white matter in the brain and severe psychomotor retardation, usually leading to death at a young age.[12][20] The loss of aspartoacylase activity leads to the buildup of N-acetyl-L-aspartate in the brain and an increase in urine concentration by up to 60 times normal levels.[19] Though the exact mechanism of how loss of aspartoacylase activity leads to Canavan disease is not fully understood, there are two primary competing explanations. The first is that it leads to defective myelin synthesis due to a deficiency of acetyl-CoA derived from the acetate product.[20] Another explanation is that the elevated levels of N-acetyl-l-aspartate interfere with its normal brain osmoregulatory mechanism leading to osmotic disequilibrium.[21]
There are over 70 reported mutations of this enzyme, but the most common ones are the amino acid substitutions E285A and A305E.[12] E285A reduces activity of aspartoacylase down to as low as 0.3% of its normal function and is found in 98% of cases with Ashkenazi Jewish ancestry.[22] The mutation A305E is found in about 40% of non-Jewish patients and reduces activity to about 10%.[22] Of these two mutations, a crystal structure of the E285A mutant has been taken, showing that the loss of the hydrogen bonding from glutamate leads to a conformational change that distorts the active site and alters the substrate binding, leading to the much lower catalytic activity.[12]
Distortion of the active site caused by the E285A mutation. Wild type ASPA is on the left (2O4H[5]) and E285A on the right (4NFR[12]).
^The enzyme is also known as N-acetylaspartate amidohydrolase, acetyl-aspartic deaminase or acylase II[6]
Referencesedit
^ abcGRCh38: Ensembl release 89: ENSG00000108381 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000020774 - Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ abcdefghBitto E, Bingman CA, Wesenberg GE, McCoy JG, Phillips GN (January 2007). "Structure of aspartoacylase, the brain enzyme impaired in Canavan disease". Proceedings of the National Academy of Sciences of the United States of America. 104 (2): 456–61. doi:10.1073/pnas.0607817104. PMC1766406. PMID 17194761.
^"Aspartoacylase (EC 3.5.1.15)". biocyc.org. from the original on 22 July 2022. Retrieved 2022-07-22.
^Birnbaum SM (1955). [12] Aminoacylase. Methods in Enzymology. Vol. 2. pp. 115–119. doi:10.1016/S0076-6879(55)02176-9. ISBN9780121818029. {{cite book}}: |journal= ignored (help)
^Birnbaum SM, Levintow L, Kingsley RB, Greenstein JP (January 1952). "Specificity of amino acid acylases". The Journal of Biological Chemistry. 194 (1): 455–70. doi:10.1016/S0021-9258(18)55898-1. PMID 14927637.
^Le Coq J, An HJ, Lebrilla C, Viola RE (May 2006). "Characterization of human aspartoacylase: the brain enzyme responsible for Canavan disease". Biochemistry. 45 (18): 5878–84. doi:10.1021/bi052608w. PMC2566822. PMID 16669630.
^Hershfield JR, Pattabiraman N, Madhavarao CN, Namboodiri MA (May 2007). "Mutational analysis of aspartoacylase: implications for Canavan disease". Brain Research. 1148: 1–14. doi:10.1016/j.brainres.2007.02.069. PMC1933483. PMID 17391648.
^Herga S, Berrin JG, Perrier J, Puigserver A, Giardina T (October 2006). "Identification of the zinc binding ligands and the catalytic residue in human aspartoacylase, an enzyme involved in Canavan disease". FEBS Letters. 580 (25): 5899–904. doi:10.1016/j.febslet.2006.09.056. PMID 17027983. S2CID 41351955.
^ abcdefWijayasinghe YS, Pavlovsky AG, Viola RE (August 2014). "Aspartoacylase catalytic deficiency as the cause of Canavan disease: a structural perspective". Biochemistry. 53 (30): 4970–8. doi:10.1021/bi500719k. PMID 25003821.
^ abcdefLe Coq J, Pavlovsky A, Malik R, Sanishvili R, Xu C, Viola RE (March 2008). "Examination of the mechanism of human brain aspartoacylase through the binding of an intermediate analogue". Biochemistry. 47 (11): 3484–92. doi:10.1021/bi702400x. PMC2666850. PMID 18293939.
^ abZhang C, Liu X, Xue Y (January 2012). "A general acid–general base reaction mechanism for human brain aspartoacylase: A QM/MM study". Computational and Theoretical Chemistry. 980: 85–91. doi:10.1016/j.comptc.2011.11.023.
^ abMoffett JR, Arun P, Ariyannur PS, Namboodiri AM (December 2013). "N-Acetylaspartate reductions in brain injury: impact on post-injury neuroenergetics, lipid synthesis, and protein acetylation". Frontiers in Neuroenergetics. 5: 11. doi:10.3389/fnene.2013.00011. PMC3872778. PMID 24421768.
^Hershfield JR, Madhavarao CN, Moffett JR, Benjamins JA, Garbern JY, Namboodiri A (October 2006). "Aspartoacylase is a regulated nuclear-cytoplasmic enzyme". FASEB Journal. 20 (12): 2139–41. doi:10.1096/fj.05-5358fje. PMID 16935940. S2CID 36296718.
^Chakraborty G, Mekala P, Yahya D, Wu G, Ledeen RW (August 2001). "Intraneuronal N-acetylaspartate supplies acetyl groups for myelin lipid synthesis: evidence for myelin-associated aspartoacylase". Journal of Neurochemistry. 78 (4): 736–45. doi:10.1046/j.1471-4159.2001.00456.x. PMID 11520894. S2CID 23338456.
^Baslow MH (April 2002). "Evidence supporting a role for N-acetyl-L-aspartate as a molecular water pump in myelinated neurons in the central nervous system. An analytical review". Neurochemistry International. 40 (4): 295–300. doi:10.1016/s0197-0186(01)00095-x. PMID 11792458. S2CID 34902757.
^ abMoore RA, Le Coq J, Faehnle CR, Viola RE (May 2003). "Purification and preliminary characterization of brain aspartoacylase". Archives of Biochemistry and Biophysics. 413 (1): 1–8. CiteSeerX10.1.1.600.6321. doi:10.1016/s0003-9861(03)00055-9. PMID 12706335.
^ abNamboodiri AM, Peethambaran A, Mathew R, Sambhu PA, Hershfield J, Moffett JR, Madhavarao CN (June 2006). "Canavan disease and the role of N-acetylaspartate in myelin synthesis". Molecular and Cellular Endocrinology. 252 (1–2): 216–23. doi:10.1016/j.mce.2006.03.016. PMID 16647192. S2CID 12255670.
^Baslow MH, Guilfoyle DN (April 2013). "Canavan disease, a rare early-onset human spongiform leukodystrophy: insights into its genesis and possible clinical interventions". Biochimie. 95 (4): 946–56. doi:10.1016/j.biochi.2012.10.023. PMID 23151389.
^ abZano S, Wijayasinghe YS, Malik R, Smith J, Viola RE (January 2013). "Relationship between enzyme properties and disease progression in Canavan disease". Journal of Inherited Metabolic Disease. 36 (1): 1–6. doi:10.1007/s10545-012-9520-z. PMID 22850825. S2CID 34211521.
Overview of all the structural information available in the PDB for UniProt: P45381 (Aspartoacylase) at the PDBe-KB.
December 14, 2023
aspartoacylase, hydrolytic, enzyme, also, called, aminoacylase, aspa, other, names, that, humans, encoded, aspa, gene, aspa, catalyzes, deacylation, acetyl, aspartate, acetylaspartate, into, aspartate, acetate, zinc, dependent, hydrolase, that, promotes, depro. Aspartoacylase is a hydrolytic enzyme EC 3 5 1 15 also called aminoacylase II ASPA and other names a that in humans is encoded by the ASPA gene ASPA catalyzes the deacylation of N acetyl l aspartate N acetylaspartate into aspartate and acetate 7 8 It is a zinc dependent hydrolase that promotes the deprotonation of water to use as a nucleophile in a mechanism analogous to many other zinc dependent hydrolases 9 It is most commonly found in the brain where it controls the levels of N acetyl l aspartate Mutations that result in loss of aspartoacylase activity are associated with Canavan disease a rare autosomal recessive neurodegenerative disease 10 ASPAAvailable structuresPDBOrtholog search PDBe RCSBList of PDB id codes4MRI 2I3C 2O4H 2Q51 2O53 4NFR 4MXU 4TNUIdentifiersAliasesASPA ACY2 ASP aspartoacylaseExternal IDsOMIM 608034 MGI 87914 HomoloGene 33 GeneCards ASPAGene location Human Chr Chromosome 17 human 1 Band17p13 2Start3 472 374 bp 1 End3 503 405 bp 1 Gene location Mouse Chr Chromosome 11 mouse 2 Band11 11 B4Start73 195 818 bp 2 End73 220 422 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed incorpus callosumkidney tubuleinternal globus pallidusjejunal mucosatrigeminal ganglioninferior ganglion of vagus nerveendothelial cellinferior olivary nucleusglomerulussubstantia nigraTop expressed inproximal tubulesciatic nervejejunumintestinal villuskidneybrown adipose tissueglobus pallidusanterior horn of spinal cordintercostal musclepontine nucleiMore reference expression dataBioGPSn aGene ontologyMolecular functionprotein binding hydrolase activity hydrolase activity acting on carbon nitrogen but not peptide bonds in linear amides metal ion binding hydrolase activity acting on ester bonds aspartoacylase activity aminoacylase activity identical protein bindingCellular componentnucleus cytoplasm cytosolBiological processmetabolism cellular amino acid biosynthetic process aspartate catabolic process central nervous system myelination positive regulation of oligodendrocyte differentiationSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez44311484EnsemblENSG00000108381ENSMUSG00000020774UniProtP45381Q8R3P0RefSeq mRNA NM 000049NM 001128085NM 023113RefSeq protein NP 000040NP 001121557NP 075602Location UCSC Chr 17 3 47 3 5 MbChr 11 73 2 73 22 MbPubMed search 3 4 WikidataView Edit HumanView Edit MouseAspartoacylaseStructure of aspartoacylase dimer Generated from 2I3C 5 IdentifiersEC no 3 5 1 15DatabasesIntEnzIntEnz viewBRENDABRENDA entryExPASyNiceZyme viewKEGGKEGG entryMetaCycmetabolic pathwayPRIAMprofilePDB structuresRCSB PDB PDBe PDBsumSearchPMCarticlesPubMedarticlesNCBIproteins Contents 1 Structure 2 Mechanism 3 Biological function 4 Disease relevance 5 See also 6 Notes 7 References 8 External linksStructure editAspartoacylase is a dimer of two identical monomers of 313 amino acids and uses a zinc cofactor in each 5 11 There are two distinct domains in each monomer the N terminal domain from residues 1 212 and the C terminal domain from residues 213 313 12 The N terminal domain of aspartoacylase is similar to that of zinc dependent hydrolases such as carboxypeptidaseA However carboxypeptidases do not have something similar to the C domain In carboxypeptidase A the active site is accessible to large substrates like the bulky C terminal residue of polypeptides whereas the C domain sterically hinders access to the active site in aspartoacylase Instead the N domain and C domain of aspartoacylase form a deep narrow channel that leads to the active site 5 The zinc cofactor is found at the active site and is held by Glu 24 His 21 and His 116 13 The substrate is held in place by Arg 63 Asn 70 Arg 71 Tyr 164 Arg 168 and Tyr 288 5 The zinc cofactor is used to lower the pKa of a ligated water molecule so that an attack on N acetyl L aspartate may occur and to stabilize the resulting tetrahedral intermediate along with Arg 63 and Glu 178 13 nbsp A monomer of aspartoacylase with the N domain in green C domain in yellow and zinc cofactor in red Generated from 2I3C 5 nbsp Active site of aspartoacylase with a bound N phosphonamidate L aspartate This is a tetrahedral intermediate analogue with phosphorus replacing the attacked carbon In the structure zinc Arg 63 and Glu 178 are stabilizing the tetrahedral intermediate Generated from 2O4H 13 Mechanism editThere are two types of possible mechanisms for zinc dependent hydrolases depending on what is the nucleophile The first uses deprotonated water and the second attacks with an aspartate or glutamate first forming an anhydride 14 Aspartoacylase follows the deprotonated water mechanism 13 Zinc lowers the pKa of a ligated water molecule and the reaction proceeds via an attack on N acetyl l aspartate when the water molecule is deprotonated by Glu 178 5 This leads to a tetrahedral intermediate that is stabilized by the zinc Arg 63 and Glu 178 13 Finally the carbonyl is then reformed the bond with nitrogen is broken and the nitrogen is protonated by the proton taken by Glu 178 all in one concerted step 14 nbsp Aspartoacylase mechanism 13 All the coordinating residues are not shown for clarity Biological function editAspartoacylase is used to metabolize N acetyl L aspartate by catalyzing its deacylation Aspartoacylase prevents the buildup of N acetyl L aspartate in the brain It is believed that controlling N acetyl L aspartate levels is essential for developing and maintaining white matter 5 It is not known why so much N acetyl L aspartate is produced in the brain nor what its primary function is 15 However one hypothesis is that it is potentially used as a chemical reservoir that can be tapped into for acetate for acetyl CoA synthesis or aspartate for glutamate synthesis 15 16 This way N acetyl L aspartate can be used to transport these precursor molecules and aspartoacylase is used to release them For example N acetyl L aspartate produced in neurons can be transported into oligodendrocytes and the acetate released can be used for myelin synthesis 12 17 Another hypothesis is that N acetyl L aspartate is essential osmolyte that acts as a molecular water pump that helps maintain a proper fluid balance in the brain 18 Disease relevance editMutations that lead to loss of aspartoacylase activity have been identified as the cause of Canavan disease 19 Canavan disease is a rare autosomal recessive disorder that causes spongy degeneration of the white matter in the brain and severe psychomotor retardation usually leading to death at a young age 12 20 The loss of aspartoacylase activity leads to the buildup of N acetyl L aspartate in the brain and an increase in urine concentration by up to 60 times normal levels 19 Though the exact mechanism of how loss of aspartoacylase activity leads to Canavan disease is not fully understood there are two primary competing explanations The first is that it leads to defective myelin synthesis due to a deficiency of acetyl CoA derived from the acetate product 20 Another explanation is that the elevated levels of N acetyl l aspartate interfere with its normal brain osmoregulatory mechanism leading to osmotic disequilibrium 21 There are over 70 reported mutations of this enzyme but the most common ones are the amino acid substitutions E285A and A305E 12 E285A reduces activity of aspartoacylase down to as low as 0 3 of its normal function and is found in 98 of cases with Ashkenazi Jewish ancestry 22 The mutation A305E is found in about 40 of non Jewish patients and reduces activity to about 10 22 Of these two mutations a crystal structure of the E285A mutant has been taken showing that the loss of the hydrogen bonding from glutamate leads to a conformational change that distorts the active site and alters the substrate binding leading to the much lower catalytic activity 12 nbsp Distortion of the active site caused by the E285A mutation Wild type ASPA is on the left 2O4H 5 and E285A on the right 4NFR 12 See also edit nbsp Biology portalAspartic acid Neurodegeneration Enzyme deficiencyNotes edit The enzyme is also known as N acetylaspartate amidohydrolase acetyl aspartic deaminase or acylase II 6 References edit a b c GRCh38 Ensembl release 89 ENSG00000108381 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000020774 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine a b c d e f g h Bitto E Bingman CA Wesenberg GE McCoy JG Phillips GN January 2007 Structure of aspartoacylase the brain enzyme impaired in Canavan disease Proceedings of the National Academy of Sciences of the United States of America 104 2 456 61 doi 10 1073 pnas 0607817104 PMC 1766406 PMID 17194761 Aspartoacylase EC 3 5 1 15 biocyc org Archived from the original on 22 July 2022 Retrieved 2022 07 22 Birnbaum SM 1955 12 Aminoacylase Methods in Enzymology Vol 2 pp 115 119 doi 10 1016 S0076 6879 55 02176 9 ISBN 9780121818029 a href Template Cite book html title Template Cite book cite book a journal ignored help Birnbaum SM Levintow L Kingsley RB Greenstein JP January 1952 Specificity of amino acid acylases The Journal of Biological Chemistry 194 1 455 70 doi 10 1016 S0021 9258 18 55898 1 PMID 14927637 Le Coq J An HJ Lebrilla C Viola RE May 2006 Characterization of human aspartoacylase the brain enzyme responsible for Canavan disease Biochemistry 45 18 5878 84 doi 10 1021 bi052608w PMC 2566822 PMID 16669630 Hershfield JR Pattabiraman N Madhavarao CN Namboodiri MA May 2007 Mutational analysis of aspartoacylase implications for Canavan disease Brain Research 1148 1 14 doi 10 1016 j brainres 2007 02 069 PMC 1933483 PMID 17391648 Herga S Berrin JG Perrier J Puigserver A Giardina T October 2006 Identification of the zinc binding ligands and the catalytic residue in human aspartoacylase an enzyme involved in Canavan disease FEBS Letters 580 25 5899 904 doi 10 1016 j febslet 2006 09 056 PMID 17027983 S2CID 41351955 a b c d e f Wijayasinghe YS Pavlovsky AG Viola RE August 2014 Aspartoacylase catalytic deficiency as the cause of Canavan disease a structural perspective Biochemistry 53 30 4970 8 doi 10 1021 bi500719k PMID 25003821 a b c d e f Le Coq J Pavlovsky A Malik R Sanishvili R Xu C Viola RE March 2008 Examination of the mechanism of human brain aspartoacylase through the binding of an intermediate analogue Biochemistry 47 11 3484 92 doi 10 1021 bi702400x PMC 2666850 PMID 18293939 a b Zhang C Liu X Xue Y January 2012 A general acid general base reaction mechanism for human brain aspartoacylase A QM MM study Computational and Theoretical Chemistry 980 85 91 doi 10 1016 j comptc 2011 11 023 a b Moffett JR Arun P Ariyannur PS Namboodiri AM December 2013 N Acetylaspartate reductions in brain injury impact on post injury neuroenergetics lipid synthesis and protein acetylation Frontiers in Neuroenergetics 5 11 doi 10 3389 fnene 2013 00011 PMC 3872778 PMID 24421768 Hershfield JR Madhavarao CN Moffett JR Benjamins JA Garbern JY Namboodiri A October 2006 Aspartoacylase is a regulated nuclear cytoplasmic enzyme FASEB Journal 20 12 2139 41 doi 10 1096 fj 05 5358fje PMID 16935940 S2CID 36296718 Chakraborty G Mekala P Yahya D Wu G Ledeen RW August 2001 Intraneuronal N acetylaspartate supplies acetyl groups for myelin lipid synthesis evidence for myelin associated aspartoacylase Journal of Neurochemistry 78 4 736 45 doi 10 1046 j 1471 4159 2001 00456 x PMID 11520894 S2CID 23338456 Baslow MH April 2002 Evidence supporting a role for N acetyl L aspartate as a molecular water pump in myelinated neurons in the central nervous system An analytical review Neurochemistry International 40 4 295 300 doi 10 1016 s0197 0186 01 00095 x PMID 11792458 S2CID 34902757 a b Moore RA Le Coq J Faehnle CR Viola RE May 2003 Purification and preliminary characterization of brain aspartoacylase Archives of Biochemistry and Biophysics 413 1 1 8 CiteSeerX 10 1 1 600 6321 doi 10 1016 s0003 9861 03 00055 9 PMID 12706335 a b Namboodiri AM Peethambaran A Mathew R Sambhu PA Hershfield J Moffett JR Madhavarao CN June 2006 Canavan disease and the role of N acetylaspartate in myelin synthesis Molecular and Cellular Endocrinology 252 1 2 216 23 doi 10 1016 j mce 2006 03 016 PMID 16647192 S2CID 12255670 Baslow MH Guilfoyle DN April 2013 Canavan disease a rare early onset human spongiform leukodystrophy insights into its genesis and possible clinical interventions Biochimie 95 4 946 56 doi 10 1016 j biochi 2012 10 023 PMID 23151389 a b Zano S Wijayasinghe YS Malik R Smith J Viola RE January 2013 Relationship between enzyme properties and disease progression in Canavan disease Journal of Inherited Metabolic Disease 36 1 1 6 doi 10 1007 s10545 012 9520 z PMID 22850825 S2CID 34211521 External links editAspartoacylase at the U S National Library of Medicine Medical Subject Headings MeSH Overview of all the structural information available in the PDB for UniProt P45381 Aspartoacylase at the PDBe KB Retrieved from https en wikipedia org w index php title Aspartoacylase amp oldid 1172527870, wikipedia, wiki, book, books, library,
