{"title":"In silico analysis of point mutation (c.687dupC; p. Met230Hisfs∗6) in PGAM2 gene that causes Glycogen Storage Disease (GSD) Type X","authors":"Ayesha Abid , Eman Nasir , Hassaan Mehboob Awan","doi":"10.1016/j.kjs.2024.100344","DOIUrl":null,"url":null,"abstract":"<div><div>Glycogen storage disease (GSD) type X is an autosomal recessive disorder that affects skeletal muscles and is caused by PGAM-2 (Phosphoglycerate Mutase-2) enzyme deficiency. This deficiency is due to a mutation in the PGAM-2 gene at chromosome number 7p13. A novel insertion mutation (c.687dupC) was reported recently in the Pakistani population. This study aimed to computationally study the effect of that mutation at the molecular level. Several <em>in silico</em> approaches were employed to understand the molecular mechanism behind PGAM2 enzyme deficiency. Modeling the wild-type and mutant PGAM2 protein revealed an absence of an alpha helix from the c-terminus. Binding site analysis showed the absence of a critical residue, Lysine-100, from the mutant. Moreover, changes in the binding affinities, intramolecular interactions, and intermolecular interactions were also observed.</div></div>","PeriodicalId":17848,"journal":{"name":"Kuwait Journal of Science","volume":"52 1","pages":"Article 100344"},"PeriodicalIF":1.2000,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Kuwait Journal of Science","FirstCategoryId":"103","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S230741082400169X","RegionNum":4,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Glycogen storage disease (GSD) type X is an autosomal recessive disorder that affects skeletal muscles and is caused by PGAM-2 (Phosphoglycerate Mutase-2) enzyme deficiency. This deficiency is due to a mutation in the PGAM-2 gene at chromosome number 7p13. A novel insertion mutation (c.687dupC) was reported recently in the Pakistani population. This study aimed to computationally study the effect of that mutation at the molecular level. Several in silico approaches were employed to understand the molecular mechanism behind PGAM2 enzyme deficiency. Modeling the wild-type and mutant PGAM2 protein revealed an absence of an alpha helix from the c-terminus. Binding site analysis showed the absence of a critical residue, Lysine-100, from the mutant. Moreover, changes in the binding affinities, intramolecular interactions, and intermolecular interactions were also observed.
期刊介绍:
Kuwait Journal of Science (KJS) is indexed and abstracted by major publishing houses such as Chemical Abstract, Science Citation Index, Current contents, Mathematics Abstract, Micribiological Abstracts etc. KJS publishes peer-review articles in various fields of Science including Mathematics, Computer Science, Physics, Statistics, Biology, Chemistry and Earth & Environmental Sciences. In addition, it also aims to bring the results of scientific research carried out under a variety of intellectual traditions and organizations to the attention of specialized scholarly readership. As such, the publisher expects the submission of original manuscripts which contain analysis and solutions about important theoretical, empirical and normative issues.