Cargando…
Molecular modeling and analysis of human and plant endo-β-N-acetyl- glucosaminidases for mutations effects on function
Endo- β-N-acetylgucosaminidases (ENGases) are the enzymes that catalyze both hydrolysis and transglycosylation reactions. It is of interest to study ENGases because of their ability to synthesize glycopeptides. Homology models of Human, Arabidopsis thaliana and Sorghum ENGases were developed and the...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Biomedical Informatics
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4166770/ https://www.ncbi.nlm.nih.gov/pubmed/25258486 http://dx.doi.org/10.6026/97320630010507 |
_version_ | 1782335304166801408 |
---|---|
author | Choragudi, Shechinah Felice Veeramachaneni, Ganesh Kumar Raman, BV JS, Bondili |
author_facet | Choragudi, Shechinah Felice Veeramachaneni, Ganesh Kumar Raman, BV JS, Bondili |
author_sort | Choragudi, Shechinah Felice |
collection | PubMed |
description | Endo- β-N-acetylgucosaminidases (ENGases) are the enzymes that catalyze both hydrolysis and transglycosylation reactions. It is of interest to study ENGases because of their ability to synthesize glycopeptides. Homology models of Human, Arabidopsis thaliana and Sorghum ENGases were developed and their active sites marked based on information available from Arthrobacter protophormiae (PDB ID: 3FHQ) ENGase. Further, these models were docked with the natural substrate GlcNAc-Asn and the inhibitor Man(3)GlcNAc-thiazoline. The catalytic triad of Asn, Glu and Tyr (N171, E173 and Y205 of bacteria) were found to be conserved across the phyla. The crucial Y299F mutation showing 3 times higher transglycosylation activity than in wild type Endo-A is known. The hydrolytic activity remained unchanged in bacteria, while the transglycosylation activity increased. This Y to F change is found to be naturally evolved and should be attributing higher transglycosylation rates in human and Arabidopsis thaliana ENGases. Ligand interactions Ligplots revealed the interaction of amino acids with hydrophobic side chains and polar uncharged side chain amino acids. Thus, structure based molecular model-ligand interactions provide insights into the catalytic mechanism of ENGases and assist in the rational engineering of ENGases. |
format | Online Article Text |
id | pubmed-4166770 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Biomedical Informatics |
record_format | MEDLINE/PubMed |
spelling | pubmed-41667702014-09-25 Molecular modeling and analysis of human and plant endo-β-N-acetyl- glucosaminidases for mutations effects on function Choragudi, Shechinah Felice Veeramachaneni, Ganesh Kumar Raman, BV JS, Bondili Bioinformation Hypothesis Endo- β-N-acetylgucosaminidases (ENGases) are the enzymes that catalyze both hydrolysis and transglycosylation reactions. It is of interest to study ENGases because of their ability to synthesize glycopeptides. Homology models of Human, Arabidopsis thaliana and Sorghum ENGases were developed and their active sites marked based on information available from Arthrobacter protophormiae (PDB ID: 3FHQ) ENGase. Further, these models were docked with the natural substrate GlcNAc-Asn and the inhibitor Man(3)GlcNAc-thiazoline. The catalytic triad of Asn, Glu and Tyr (N171, E173 and Y205 of bacteria) were found to be conserved across the phyla. The crucial Y299F mutation showing 3 times higher transglycosylation activity than in wild type Endo-A is known. The hydrolytic activity remained unchanged in bacteria, while the transglycosylation activity increased. This Y to F change is found to be naturally evolved and should be attributing higher transglycosylation rates in human and Arabidopsis thaliana ENGases. Ligand interactions Ligplots revealed the interaction of amino acids with hydrophobic side chains and polar uncharged side chain amino acids. Thus, structure based molecular model-ligand interactions provide insights into the catalytic mechanism of ENGases and assist in the rational engineering of ENGases. Biomedical Informatics 2014-08-30 /pmc/articles/PMC4166770/ /pubmed/25258486 http://dx.doi.org/10.6026/97320630010507 Text en © 2014 Biomedical Informatics This is an open-access article, which permits unrestricted use, distribution, and reproduction in any medium, for non-commercial purposes, provided the original author and source are credited. |
spellingShingle | Hypothesis Choragudi, Shechinah Felice Veeramachaneni, Ganesh Kumar Raman, BV JS, Bondili Molecular modeling and analysis of human and plant endo-β-N-acetyl- glucosaminidases for mutations effects on function |
title | Molecular modeling and analysis of human and plant endo-β-N-acetyl- glucosaminidases for mutations effects on function |
title_full | Molecular modeling and analysis of human and plant endo-β-N-acetyl- glucosaminidases for mutations effects on function |
title_fullStr | Molecular modeling and analysis of human and plant endo-β-N-acetyl- glucosaminidases for mutations effects on function |
title_full_unstemmed | Molecular modeling and analysis of human and plant endo-β-N-acetyl- glucosaminidases for mutations effects on function |
title_short | Molecular modeling and analysis of human and plant endo-β-N-acetyl- glucosaminidases for mutations effects on function |
title_sort | molecular modeling and analysis of human and plant endo-β-n-acetyl- glucosaminidases for mutations effects on function |
topic | Hypothesis |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4166770/ https://www.ncbi.nlm.nih.gov/pubmed/25258486 http://dx.doi.org/10.6026/97320630010507 |
work_keys_str_mv | AT choragudishechinahfelice molecularmodelingandanalysisofhumanandplantendobnacetylglucosaminidasesformutationseffectsonfunction AT veeramachaneniganeshkumar molecularmodelingandanalysisofhumanandplantendobnacetylglucosaminidasesformutationseffectsonfunction AT ramanbv molecularmodelingandanalysisofhumanandplantendobnacetylglucosaminidasesformutationseffectsonfunction AT jsbondili molecularmodelingandanalysisofhumanandplantendobnacetylglucosaminidasesformutationseffectsonfunction |