Glycogen debranching enzyme: Difference between revisions

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Revision as of 01:47, 11 March 2018

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[[File:Hypothesized substraight binding ___location.png]]

The structure of the ''Candida glabrata'' GDE has been reported.<ref>{{Cite journal|last=Zhai|first=Liting|last2=Feng|first2=Lingling|last3=Xia|first3=Lin|last4=Yin|first4=Huiyong|last5=Xiang|first5=Song|date=2016-04-18|title=Crystal structure of glycogen debranching enzyme and insights into its catalysis and disease-causing mutations|url=https://www.nature.com/articles/ncomms11229|journal=Nature Communications|language=en|volume=7|pages=ncomms11229|doi=10.1038/ncomms11229}}</ref>. The structure revealed that distinct domains in GDE encode the glucanotransferase and glucosidase activities. Their catalyses are similar to that of alpha-amylase and glucoamylase, respectively. Their active sites are selective towards the respective substrates, ensuring proper activation of GDE. Besides the active sites GDE have additional binding sites for glycogen, which are important for its recruitment to glycogen. Mapping the disease-causing mutations onto the GDE structure provided insights into glycogen storage disease type III.

== Genetic Location___location ==

The official name for the gene is “amylo"amylo- α- 1,6- glucosidase, 4- α- glucanotransferase",” with the official symbol AGL. AGL is an autosomal gene found on chromosome lp21.<ref name=Hondoh/> The AGL gene provides instructions for making several different versions, known as isoforms, of the glycogen debranching enzyme. These isoforms vary by size and are expressed in different tissues, such as liver and muscle. This gene has been studied in great detail, because mutation at this gene is the cause of Glycogen Storage Disease Type III.<ref name=Gene/>

The gene is 85 kb long, has 35 [[exon]]s and encodes for a 7.0 kb- mRNA. Translation of the gene begins at exon 3,which encodes for the first 27 amino acids of the AGL gene, because the first two exons (68kb) contain the 5’5' untranslated region. Exons 4-35 encode the remaining 1505 amino acids of the AGL gene.<ref name= Bao/>

Studies produced by the department of pediatrics at Duke University suggest that the human AGL gene contains at minimum 2 promotor regions, sites where the transcription of the gene begins, that result in differential expression of isoform, different forms of the same protein, mRNAs in a manner that is specific for different tissues.<ref name = Gillard /><ref name=Ding />

== Clinical Significancesignificance ==

{{Main|Glycogen storage disease type III}}

When GDE activity is compromised, the body cannot effectively release stored glycogen, type III Glycogen Storage Disease (debrancher deficiency), an autosomal recessive disorder, can result. In GSD III glycogen breakdown is incomplete and there is accumulation of abnormal glycogen with short outer branches.<ref name= Monga/>