Non-synonymous single nucleotide polymorphisms of ATG5 destabilize ATG12–ATG5/ATG16L1 complex: An enzyme with E3 like activity of ubiquitin conjugation system

Vij, Avni; Yennamalli, Ragothaman M.; Changotra, Harish

doi:10.1016/j.mgene.2017.04.008

Cited by 7 publications

(7 citation statements)

References 56 publications

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“…PDBsum is a web‐based database providing largely illustrative depictions of macromolecular structures accessible in PDB. The wild (3V6O) and mutant structures of LEPR were submitted in PDBsum the output showed the secondary structure of the protein . FT site server was used for the analysis of the binding site of the LEPR protein for ligand with 94% accuracy from investigational evidence.…”

Section: Methodsmentioning

confidence: 99%

“…The wild (3V6O) and mutant structures of LEPR were submitted in PDBsum the output showed the secondary structure of the protein. 47 FT site server was used for the analysis of the binding site of the LEPR protein for ligand with 94% accuracy from investigational evidence. This binding site analysis for LEPR protein is necessary to expose the structural-functional relationship and for protein engineering.…”

Section: Secondary Structure Analysis and Analysis Of Binding Sitementioning

confidence: 99%

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Computational and artificial neural network based study of functional SNPs of human LEPR protein associated with reproductive function

Muruganandhan

Manian

2019

J of Cellular Biochemistry

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Genetic polymorphisms are mostly associated with inherited diseases, detecting and analyzing the biological significance of functional single‐nucleotide polymorphisms (SNPs) using wet laboratory experiments is an arduous task hence the computational analysis of putative SNPs is essential before conducting a study on a large population. SNP in the leptin receptor (LEPR) could result in the retention of intracellular signalling due to the structural and functional instability of the receptor causing abnormal reproductive function in human. In this first comprehensive computational analysis of LEPR gene mutation, we have identified and analyzed the functional consequence and structural significance of the SNPs in LEPR using recently developed several computational algorithms. Thirteen deleterious mutations such as W13C, S93G, I232R, Q307H, Y354C, E497A, Q571H, R612H, K656N, T690A, T699M V741M, and L760R were identified in the LEPR gene coding region. Backpropagation algorithm has been developed to forestall the deleterious nature of SNP and to validate the outcome of the tested computational tools. From ConSurf prediction three SNPs (Q571H, R612H, and T699M) were highly conserved on LEPR protein and the most deleterious variant R612H had one hydrogen bond abolished and severely reduced protein stability. Molecular docking suggested that the mutant (R612H) LEPR had lowest binding energy than native LEPR with the ligand molecule. Thus the energetically destructive changeover of ARG to HIS in R612H could possibly affect the LEPR protein structural stability and functional constancy due to interruption in the amino acid interactions and could result in reproductive disorders in human and increases the complication in obstetric and pregnancy outcome.

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Section: Methodsmentioning

confidence: 99%

Section: Secondary Structure Analysis and Analysis Of Binding Sitementioning

confidence: 99%

Computational and artificial neural network based study of functional SNPs of human LEPR protein associated with reproductive function

Muruganandhan

Manian

2019

J of Cellular Biochemistry

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“…Also, rs77859116 leads to destabilizing ATG5. Both of these interferences can lead to decreased autophagy and might be a clue for the carcinogenesis of this polymorphism 62 . The rs510432 is a polymorphism upstream of ATG5 63 .…”

Section: Discussionmentioning

confidence: 99%

Autophagy‐related genes polymorphism in hepatitis B virus‐associated hepatocellular carcinoma: A systematic review

Yousefi,

Tabibzadeh,

Jawaziri

et al. 2024

Immunity Inflam & Disease

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BackgroundChronic hepatitis B (CHB) virus is the most common risk factor for developing liver malignancy. Autophagy is an essential element in human cell maintenance. Several studies have demonstrated that autophagy plays a vital role in liver cancer at different stages. In this systematic review, we intend to investigate the role of polymorphism and mutations of autophagy‐related genes (ATGs) in the pathogenesis and carcinogenesis of the hepatitis B virus (HBV).Materials and MethodsThe search was conducted in online databases (Web of Science, PubMed, and Scopus) using Viruses, Infections, Polymorphism, Autophagy, and ATG. The study was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses criteria.ResultsThe primary search results led to 422 studies. By screening and eligibility evaluation, only four studies were relevant. The most important polymorphisms in hepatocellular carcinoma were rs2241880 in ATG16L1, rs77859116, rs510432, and rs548234 in ATG5. Furthermore, some polymorphisms are associated with an increased risk of HBV infection including, rs2241880 in ATG16L1 and rs6568431 in ATG5.ConclusionThe current study highlights the importance of rs2241880 in ATG16L1 and rs77859116, rs510432, and rs548234 in ATG5 for HBV‐induced HCC. Additionally, some mutations in ATG16L1 and ATG5 were important in risk of HBV infection. The study highlights the gap of knowledge in the field of ATG polymorphisms in HBV infection and HBV‐induced HCC.

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“…ATG5 interacts with various other protein partners during the process of autophagy, thus any alteration in the protein due to alteration in the coding nucleotides will subsequently affect its interaction as well. Moreover, the destability of ATG12–ATG5/ATG16L1 complex due to ATG5 nonsynonymous SNPs is reported 171 . A novel heterozygous variant in ATG5 , 106774459T > A has been found in Parkinson's disease patients in a study that significantly increased the transcriptional activities of the promoter of the ATG5 gene.…”

Section: Atg5 Polymorphisms In Various Diseasesmentioning

confidence: 99%

“…Moreover, the destability of ATG12-ATG5/ ATG16L1 complex due to ATG5 nonsynonymous SNPs is reported. 171 A novel heterozygous variant in ATG5, 106774459T > A has been found in Parkinson's disease patients in a study that significantly increased the transcriptional activities of the promoter of the ATG5 gene. In these patients, elevated ATG5 expression levels were also observed.…”

Section: Atg5 Polymorphisms In Various Diseasesmentioning

confidence: 99%

ATG5: A central autophagy regulator implicated in various human diseases

Changotra

Kaur

Yadav

et al. 2022

Cell Biochemistry & Function

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Autophagy, an intracellular conserved degradative process, plays a central role in the renewal/recycling of a cell to maintain the homeostasis of nutrients and energy within the cell. ATG5, a key component of autophagy, regulates the formation of the autophagosome, a hallmark of autophagy. ATG5 binds with ATG12 and ATG16L1 resulting in E3 like ligase complex, which is necessary for autophagosome expansion. Available data suggest that ATG5 is indispensable for autophagy and has an imperative role in several essential biological processes. Moreover, ATG5 has also been demonstrated to possess autophagy‐independent functions that magnify its significance and therapeutic potential. ATG5 interacts with various molecules for the execution of different processes implicated during physiological and pathological conditions. Furthermore, ATG5 genetic variants are associated with various ailments. This review discusses various autophagy‐dependent and autophagy‐independent roles of ATG5, highlights its various deleterious genetic variants reported until now, and various studies supporting it as a potential drug target.

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Non-synonymous single nucleotide polymorphisms of ATG5 destabilize ATG12–ATG5/ATG16L1 complex: An enzyme with E3 like activity of ubiquitin conjugation system

Cited by 7 publications

References 56 publications

Computational and artificial neural network based study of functional SNPs of human LEPR protein associated with reproductive function

Computational and artificial neural network based study of functional SNPs of human LEPR protein associated with reproductive function

Autophagy‐related genes polymorphism in hepatitis B virus‐associated hepatocellular carcinoma: A systematic review

ATG5: A central autophagy regulator implicated in various human diseases

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