Conformational motions regulate phosphoryl transfer in related protein tyrosine phosphatases
Identifieur interne : 001407 ( Main/Exploration ); précédent : 001406; suivant : 001408Conformational motions regulate phosphoryl transfer in related protein tyrosine phosphatases
Auteurs : Sean K. Whittier [États-Unis] ; Alvan C. Hengge [États-Unis] ; J. Patrick Loria [États-Unis]Source :
- Science (New York, N.Y.) [ 0036-8075 ] ; 2013.
Abstract
Many studies have implicated a role for conformational motions during the catalytic cycle, acting to optimize the binding pocket or facilitate product release, but a more intimate role in the chemical reaction has not been described. We address this by monitoring active-site loop motion in two protein tyrosine phosphatases (PTPs) using NMR spectroscopy. The PTPs, YopH and PTP1B, have very different catalytic rates, however we find in both that the active-site loop closes to its catalytically competent position at rates that mirror the phosphotyrosine cleavage kinetics. This loop contains the catalytic acid, suggesting that loop closure occurs concomitantly with the protonation of the leaving group tyrosine and explains the different kinetics of two otherwise chemically and mechanistically indistinguishable enzymes.
Url:
DOI: 10.1126/science.1241735
PubMed: 23970698
PubMed Central: 4078984
Affiliations:
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Patrick Loria</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Chemistry, Yale University, 225 Prospect St. New Haven, CT 06520</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Connecticut</region></placeName><wicri:cityArea>Department of Chemistry, Yale University, 225 Prospect St. New Haven</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="A3">Department of Molecular Biophysics and Biochemistry, Yale University, 260 Whitney Ave, New Haven, CT 06520</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Connecticut</region></placeName><wicri:cityArea>Department of Molecular Biophysics and Biochemistry, Yale University, 260 Whitney Ave, New Haven</wicri:cityArea></affiliation></author></analytic><series><title level="j">Science (New York, N.Y.)</title><idno type="ISSN">0036-8075</idno><idno type="eISSN">1095-9203</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">Many studies have implicated a role for conformational motions during the catalytic cycle, acting to optimize the binding pocket or facilitate product release, but a more intimate role in the chemical reaction has not been described. We address this by monitoring active-site loop motion in two protein tyrosine phosphatases (PTPs) using NMR spectroscopy. The PTPs, YopH and PTP1B, have very different catalytic rates, however we find in both that the active-site loop closes to its catalytically competent position at rates that mirror the phosphotyrosine cleavage kinetics. This loop contains the catalytic acid, suggesting that loop closure occurs concomitantly with the protonation of the leaving group tyrosine and explains the different kinetics of two otherwise chemically and mechanistically indistinguishable enzymes.</p></div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Connecticut</li><li>Utah</li></region></list><tree><country name="États-Unis"><region name="Connecticut"><name sortKey="Whittier, Sean K" sort="Whittier, Sean K" uniqKey="Whittier S" first="Sean K." last="Whittier">Sean K. Whittier</name></region><name sortKey="Hengge, Alvan C" sort="Hengge, Alvan C" uniqKey="Hengge A" first="Alvan C." last="Hengge">Alvan C. Hengge</name><name sortKey="Loria, J Patrick" sort="Loria, J Patrick" uniqKey="Loria J" first="J. Patrick" last="Loria">J. Patrick Loria</name><name sortKey="Loria, J Patrick" sort="Loria, J Patrick" uniqKey="Loria J" first="J. Patrick" last="Loria">J. Patrick Loria</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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