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From Proteopedia
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/ASM_HUMAN ASM_HUMAN]] Converts sphingomyelin to ceramide (PubMed:1840600, PubMed:18815062). Also has phospholipase C activities toward 1,2-diacylglycerolphosphocholine and 1,2-diacylglycerolphosphoglycerol.<ref>PMID:1840600</ref> <ref>PMID:18815062</ref> Isoform 2 lacks residues that bind the cofactor Zn(2+) and has no enzyme activity.<ref>PMID:1840600</ref> Isoform 3 lacks residues that bind the cofactor Zn(2+) and has no enzyme activity.<ref>PMID:1840600</ref> | [[http://www.uniprot.org/uniprot/ASM_HUMAN ASM_HUMAN]] Converts sphingomyelin to ceramide (PubMed:1840600, PubMed:18815062). Also has phospholipase C activities toward 1,2-diacylglycerolphosphocholine and 1,2-diacylglycerolphosphoglycerol.<ref>PMID:1840600</ref> <ref>PMID:18815062</ref> Isoform 2 lacks residues that bind the cofactor Zn(2+) and has no enzyme activity.<ref>PMID:1840600</ref> Isoform 3 lacks residues that bind the cofactor Zn(2+) and has no enzyme activity.<ref>PMID:1840600</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Acid sphingomyelinase (ASM) hydrolyzes sphingomyelin to ceramide and phosphocholine, essential components of myelin in neurons. Genetic alterations in ASM lead to ASM deficiency (ASMD) and have been linked to Niemann-Pick disease types A and B. Olipudase alfa, a recombinant form of human ASM, is being developed as enzyme replacement therapy to treat the non-neurological manifestations of ASMD. Here we present the human ASM holoenzyme and product bound structures encompassing all of the functional domains. The catalytic domain has a metallophosphatase fold, and two zinc ions and one reaction product phosphocholine are identified in a histidine-rich active site. The structures reveal the underlying catalytic mechanism, in which two zinc ions activate a water molecule for nucleophilic attack of the phosphodiester bond. Docking of sphingomyelin provides a model that allows insight into the selectivity of the enzyme and how the ASM domains collaborate to complete hydrolysis. Mapping of known mutations provides a basic understanding on correlations between enzyme dysfunction and phenotypes observed in ASMD patients. | ||
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| + | Human acid sphingomyelinase structures provide insight to molecular basis of Niemann-Pick disease.,Zhou YF, Metcalf MC, Garman SC, Edmunds T, Qiu H, Wei RR Nat Commun. 2016 Oct 11;7:13082. doi: 10.1038/ncomms13082. PMID:27725636<ref>PMID:27725636</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5i85" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 03:37, 10 December 2016
aSMase with zinc and phosphocholine
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