Impact of genetic variation on three dimensional structure and function of proteins.

The Protein Data Bank (PDB; http://wwpdb.org) was established in 1971 as the first open access digital data resource in biology with seven protein structures as its initial holdings. The global PDB archive now contains more than 126,000 experimentally determined atomic level three-dimensional (3D) s...

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Main Authors: Roshni Bhattacharya, Peter W Rose, Stephen K Burley, Andreas Prlić
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5351996?pdf=render
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author Roshni Bhattacharya
Peter W Rose
Stephen K Burley
Andreas Prlić
author_facet Roshni Bhattacharya
Peter W Rose
Stephen K Burley
Andreas Prlić
author_sort Roshni Bhattacharya
collection DOAJ
description The Protein Data Bank (PDB; http://wwpdb.org) was established in 1971 as the first open access digital data resource in biology with seven protein structures as its initial holdings. The global PDB archive now contains more than 126,000 experimentally determined atomic level three-dimensional (3D) structures of biological macromolecules (proteins, DNA, RNA), all of which are freely accessible via the Internet. Knowledge of the 3D structure of the gene product can help in understanding its function and role in disease. Of particular interest in the PDB archive are proteins for which 3D structures of genetic variant proteins have been determined, thus revealing atomic-level structural differences caused by the variation at the DNA level. Herein, we present a systematic and qualitative analysis of such cases. We observe a wide range of structural and functional changes caused by single amino acid differences, including changes in enzyme activity, aggregation propensity, structural stability, binding, and dissociation, some in the context of large assemblies. Structural comparison of wild type and mutated proteins, when both are available, provide insights into atomic-level structural differences caused by the genetic variation.
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spelling doaj.art-6aae8dfc7f7a461da22980ac7a9f82552022-12-22T02:46:18ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01123e017135510.1371/journal.pone.0171355Impact of genetic variation on three dimensional structure and function of proteins.Roshni BhattacharyaPeter W RoseStephen K BurleyAndreas PrlićThe Protein Data Bank (PDB; http://wwpdb.org) was established in 1971 as the first open access digital data resource in biology with seven protein structures as its initial holdings. The global PDB archive now contains more than 126,000 experimentally determined atomic level three-dimensional (3D) structures of biological macromolecules (proteins, DNA, RNA), all of which are freely accessible via the Internet. Knowledge of the 3D structure of the gene product can help in understanding its function and role in disease. Of particular interest in the PDB archive are proteins for which 3D structures of genetic variant proteins have been determined, thus revealing atomic-level structural differences caused by the variation at the DNA level. Herein, we present a systematic and qualitative analysis of such cases. We observe a wide range of structural and functional changes caused by single amino acid differences, including changes in enzyme activity, aggregation propensity, structural stability, binding, and dissociation, some in the context of large assemblies. Structural comparison of wild type and mutated proteins, when both are available, provide insights into atomic-level structural differences caused by the genetic variation.http://europepmc.org/articles/PMC5351996?pdf=render
spellingShingle Roshni Bhattacharya
Peter W Rose
Stephen K Burley
Andreas Prlić
Impact of genetic variation on three dimensional structure and function of proteins.
PLoS ONE
title Impact of genetic variation on three dimensional structure and function of proteins.
title_full Impact of genetic variation on three dimensional structure and function of proteins.
title_fullStr Impact of genetic variation on three dimensional structure and function of proteins.
title_full_unstemmed Impact of genetic variation on three dimensional structure and function of proteins.
title_short Impact of genetic variation on three dimensional structure and function of proteins.
title_sort impact of genetic variation on three dimensional structure and function of proteins
url http://europepmc.org/articles/PMC5351996?pdf=render
work_keys_str_mv AT roshnibhattacharya impactofgeneticvariationonthreedimensionalstructureandfunctionofproteins
AT peterwrose impactofgeneticvariationonthreedimensionalstructureandfunctionofproteins
AT stephenkburley impactofgeneticvariationonthreedimensionalstructureandfunctionofproteins
AT andreasprlic impactofgeneticvariationonthreedimensionalstructureandfunctionofproteins