About: Rheostat positions: A new classification of protein positions relevant to pharmacogenomics

Facets (new session)
Description
Metadata
Settings
- owl:sameAs
- Inference Rule:

About: Rheostat positions: A new classification of protein positions relevant to pharmacogenomics Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Rheostat positions: A new classification of protein positions relevant to pharmacogenomics
Creator	Fenton, Aron Page, Braelyn Spellman-Kruse, Arianna Swint-Kruse, Liskin Hagenbuch, •
topic	covid:f3a7bbd59d8d56de9e5357f1b2f57b780a9e55f3#this
Source	Medline; PMC
abstract	To achieve the full potential of pharmacogenomics, one must accurately predict the functional outcomes that arise from amino acid substitutions in proteins. Classically, researchers have focused on understanding the consequences of individual substitutions. However, literature surveys have shown that most substitutions were created at evolutionarily conserved positions. Awareness of this bias leads to a shift in perspective, from considering the outcomes of individual substitutions to understanding the roles of individual protein positions. Conserved positions tend to act as “toggle” switches, with most substitutions abolishing function. However, nonconserved positions have been found equally capable of affecting protein function. Indeed, many nonconserved positions act like functional dimmer switches (“rheostat” positions): this is revealed when multiple substitutions are made at a single position. Each substitution has a different functional outcome; the set of substitutions spans a range of outcomes. Finally, some nonconserved positions appear neutral, capable of accommodating all amino acid types without modifying function. This paper reviews the currently-known properties of rheostat positions, with examples shown for pyruvate kinase, organic anion transporting polypeptide 1B1, the beta-lactamase inhibitory protein, and angiotensin-converting enzyme 2. Outcomes observed for rheostat positions have implications for the rational design of drug analogs and allosteric drugs. Furthermore, this new framework—comprising three types of protein positions—provides a new approach to interpreting disease and population-based databases of amino acid changes. In conclusion, although a full understanding of substitution outcomes at rheostat positions poses a challenge, utilization of this new frame of reference will further advance the application of pharmacogenomics.
has issue date	2020-06-07(xsd:dateTime)
bibo:doi	10.1007/s00044-020-02582-9
bibo:pmid	32641900
has license	no-cc
sha1sum (hex)	f3a7bbd59d8d56de9e5357f1b2f57b780a9e55f3
schema:url	https://doi.org/10.1007/s00044-020-02582-9
resource representing a document's title	Rheostat positions: A new classification of protein positions relevant to pharmacogenomics
has PubMed Central identifier	PMC7276102
has PubMed identifier	32641900
schema:publication	Med Chem Res
resource representing a document's body	covid:f3a7bbd59d8d56de9e5357f1b2f57b780a9e55f3#body_text
is http://vocab.deri.ie/void#inDataset of	proxy:http/ns.inria.fr/covid19/f3a7bbd59d8d56de9e5357f1b2f57b780a9e55f3
is schema:about of	named entity 'substitutions' named entity 'literature' named entity 'acid' named entity 'substitution' named entity 'perspective' named entity 'evolutionarily conserved' named entity 'DISEASE' named entity 'UNDERSTANDING' named entity 'AMINO ACID' named entity 'SINGLE' named entity 'ACT' named entity 'PROTEINS' named entity 'LIKE' named entity 'FUNCTION' named entity 'FOUND' named entity 'drug' named entity 'positions' named entity 'positions' named entity 'pharmacogenomics' named entity 'Indeed' named entity 'spans' named entity 'acid' named entity 'substitution' named entity 'rational design' named entity 'analogs' named entity 'substitutions' named entity 'angiotensin-converting enzyme 2' named entity 'protein' named entity 'amino acid' named entity 'amino acid' named entity 'angiotensin-converting enzyme 2' named entity 'rheostat' named entity 'pharmacogenomics' named entity 'rheostat' named entity 'MEDICINAL CHEMISTRY' named entity 'inhibitory' named entity 'evolution' named entity 'Rheostat' named entity 'protein' named entity 'sequence analyses' named entity 'ligand' named entity 'protein' named entity 'wild-type' named entity 'allosteric' named entity 'OATP1B1' named entity 'amino acid' named entity 'protein sequence' named entity 'rheostat' named entity 'biochemical' named entity 'allosteric ligands' named entity 'sequence analyses' named entity 'mutagenesis' named entity 'sequenced' named entity 'protein family' named entity 'rheostat' named entity 'rheostat' named entity 'alanine scan' named entity 'glycine' named entity 'pharmacogenomics' named entity 'substrate' named entity 'rheostat' named entity 'Rheostat' named entity 'pyruvate kinase' named entity 'enzyme' named entity 'Angiotensin-converting enzyme 2' named entity 'N-terminus' named entity 'human liver' named entity 'xaxis' named entity 'intrinsically disordered proteins' named entity 'alanine' named entity 'active site' named entity 'sequence alignments' named entity 'correlation' named entity 'rheostat' named entity 'disease-causing'

Faceted Search & Find service v1.13.91 as of Mar 24 2020

Alternative Linked Data Documents: Sponger | ODE Content Formats:

RDF

ODATA

Microdata

About

OpenLink Virtuoso version 07.20.3229 as of Jul 10 2020, on Linux (x86_64-pc-linux-gnu), Single-Server Edition (94 GB total memory)
Data on this page belongs to its respective rights holders.
Virtuoso Faceted Browser Copyright © 2009-2024 OpenLink Software