Conserved Functional Motifs and Homology Modeling to Predict Hidden Moonlighting Functional Sites

Handle URI:
http://hdl.handle.net/10754/558418
Title:
Conserved Functional Motifs and Homology Modeling to Predict Hidden Moonlighting Functional Sites
Authors:
Wong, Aloysius Tze ( 0000-0002-9105-5845 ) ; Gehring, Christoph A. ( 0000-0003-4355-4591 ) ; Irving, Helen R.
Abstract:
Moonlighting functional centers within proteins can provide them with hitherto unrecognized functions. Here, we review how hidden moonlighting functional centers, which we define as binding sites that have catalytic activity or regulate protein function in a novel manner, can be identified using targeted bioinformatic searches. Functional motifs used in such searches include amino acid residues that are conserved across species and many of which have been assigned functional roles based on experimental evidence. Molecules that were identified in this manner seeking cyclic mononucleotide cyclases in plants are used as examples. The strength of this computational approach is enhanced when good homology models can be developed to test the functionality of the predicted centers in silico, which, in turn, increases confidence in the ability of the identified candidates to perform the predicted functions. Computational characterization of moonlighting functional centers is not diagnostic for catalysis but serves as a rapid screening method, and highlights testable targets from a potentially large pool of candidates for subsequent in vitro and in vivo experiments required to confirm the functionality of the predicted moonlighting centers.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division
Citation:
Conserved Functional Motifs and Homology Modeling to Predict Hidden Moonlighting Functional Sites 2015, 3 Frontiers in Bioengineering and Biotechnology
Publisher:
Frontiers Media SA
Journal:
Frontiers in Bioengineering and Biotechnology
Issue Date:
9-Jun-2015
DOI:
10.3389/fbioe.2015.00082
Type:
Article
ISSN:
2296-4185
Additional Links:
http://www.frontiersin.org/Bioinformatics_and_Computational_Biology/10.3389/fbioe.2015.00082/abstract
Appears in Collections:
Articles; Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorWong, Aloysius Tzeen
dc.contributor.authorGehring, Christoph A.en
dc.contributor.authorIrving, Helen R.en
dc.date.accessioned2015-06-22T14:05:41Zen
dc.date.available2015-06-22T14:05:41Zen
dc.date.issued2015-06-09en
dc.identifier.citationConserved Functional Motifs and Homology Modeling to Predict Hidden Moonlighting Functional Sites 2015, 3 Frontiers in Bioengineering and Biotechnologyen
dc.identifier.issn2296-4185en
dc.identifier.doi10.3389/fbioe.2015.00082en
dc.identifier.urihttp://hdl.handle.net/10754/558418en
dc.description.abstractMoonlighting functional centers within proteins can provide them with hitherto unrecognized functions. Here, we review how hidden moonlighting functional centers, which we define as binding sites that have catalytic activity or regulate protein function in a novel manner, can be identified using targeted bioinformatic searches. Functional motifs used in such searches include amino acid residues that are conserved across species and many of which have been assigned functional roles based on experimental evidence. Molecules that were identified in this manner seeking cyclic mononucleotide cyclases in plants are used as examples. The strength of this computational approach is enhanced when good homology models can be developed to test the functionality of the predicted centers in silico, which, in turn, increases confidence in the ability of the identified candidates to perform the predicted functions. Computational characterization of moonlighting functional centers is not diagnostic for catalysis but serves as a rapid screening method, and highlights testable targets from a potentially large pool of candidates for subsequent in vitro and in vivo experiments required to confirm the functionality of the predicted moonlighting centers.en
dc.publisherFrontiers Media SAen
dc.relation.urlhttp://www.frontiersin.org/Bioinformatics_and_Computational_Biology/10.3389/fbioe.2015.00082/abstracten
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.en
dc.subjectmoonlighting functional centersen
dc.subjectguanylyl/adenylyl cyclaseen
dc.subjectH-NOXen
dc.subjectsearch motifsen
dc.subjecthomology modelingen
dc.subjectmolecular dockingen
dc.titleConserved Functional Motifs and Homology Modeling to Predict Hidden Moonlighting Functional Sitesen
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.identifier.journalFrontiers in Bioengineering and Biotechnologyen
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionMonash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australiaen
kaust.authorWong, Aloysius Tzeen
kaust.authorGehring, Christoph A.en
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