The pKa value and accessibility of cysteine residues are key determinants for protein substrate discrimination by glutaredoxin.
Identifieur interne : 000593 ( Main/Exploration ); précédent : 000592; suivant : 000594The pKa value and accessibility of cysteine residues are key determinants for protein substrate discrimination by glutaredoxin.
Auteurs : Kristine Steen Jensen [Danemark] ; Jeppe T. Pedersen ; Jakob R. Winther ; Kaare TeilumSource :
- Biochemistry [ 1520-4995 ] ; 2014.
Descripteurs français
- KwdFr :
- MESH :
English descriptors
- KwdEn :
- MESH :
- chemical , metabolism : Cysteine, Glutaredoxins.
- Biocatalysis, Kinetics, Models, Molecular, Nuclear Magnetic Resonance, Biomolecular.
Abstract
The enzyme glutaredoxin catalyzes glutathione exchange, but little is known about its interaction with protein substrates. Very different proteins are substrates in vitro, and the enzyme seems to have low requirements for specific protein interactions. Here we present a systematic investigation of the interaction between human glutaredoxin 1 and glutathionylated variants of a single model protein. Thus, single cysteine variants of acyl-coenzyme A binding protein were produced creating a set of substrates in the same protein background. The rate constants for deglutathionylation differ by more than 2 orders of magnitude between the best (k1 = 1.75 × 10(5) M(-1) s(-1)) and the worst substrate (k1 = 4 × 10(2) M(-1) s(-1)). The pKa values of the substrate cysteine residues were determined by NMR spectroscopy and found to vary from 8.2 to 9.9. Rates of glutaredoxin 1-catalyzed deglutathionylation were assessed with respect to substrate cysteine pKa values, cysteine residue accessibility, local stability, and backbone dynamics. Good substrates are characterized by a combination of high accessibility of the glutathionylated site and low pKa of the cysteine residue.
DOI: 10.1021/bi4016633
PubMed: 24673564
Affiliations:
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Pedersen</name></author><author><name sortKey="Winther, Jakob R" sort="Winther, Jakob R" uniqKey="Winther J" first="Jakob R" last="Winther">Jakob R. Winther</name></author><author><name sortKey="Teilum, Kaare" sort="Teilum, Kaare" uniqKey="Teilum K" first="Kaare" last="Teilum">Kaare Teilum</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:24673564</idno><idno type="pmid">24673564</idno><idno type="doi">10.1021/bi4016633</idno><idno type="wicri:Area/Main/Corpus">000639</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000639</idno><idno type="wicri:Area/Main/Curation">000639</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000639</idno><idno type="wicri:Area/Main/Exploration">000639</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">The pKa value and accessibility of cysteine residues are key determinants for protein substrate discrimination by glutaredoxin.</title><author><name sortKey="Jensen, Kristine Steen" sort="Jensen, Kristine Steen" uniqKey="Jensen K" first="Kristine Steen" last="Jensen">Kristine Steen Jensen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biology, University of Copenhagen , Ole Maaleøs Vej 5, 2200 Copenhagen N, Denmark.</nlm:affiliation><country xml:lang="fr">Danemark</country><wicri:regionArea>Department of Biology, University of Copenhagen , Ole Maaleøs Vej 5, 2200 Copenhagen N</wicri:regionArea><wicri:noRegion>2200 Copenhagen N</wicri:noRegion></affiliation></author><author><name sortKey="Pedersen, Jeppe T" sort="Pedersen, Jeppe T" uniqKey="Pedersen J" first="Jeppe T" last="Pedersen">Jeppe T. Pedersen</name></author><author><name sortKey="Winther, Jakob R" sort="Winther, Jakob R" uniqKey="Winther J" first="Jakob R" last="Winther">Jakob R. Winther</name></author><author><name sortKey="Teilum, Kaare" sort="Teilum, Kaare" uniqKey="Teilum K" first="Kaare" last="Teilum">Kaare Teilum</name></author></analytic><series><title level="j">Biochemistry</title><idno type="eISSN">1520-4995</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Biocatalysis (MeSH)</term><term>Cysteine (metabolism)</term><term>Glutaredoxins (metabolism)</term><term>Kinetics (MeSH)</term><term>Models, Molecular (MeSH)</term><term>Nuclear Magnetic Resonance, Biomolecular (MeSH)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Biocatalyse (MeSH)</term><term>Cinétique (MeSH)</term><term>Cystéine (métabolisme)</term><term>Glutarédoxines (métabolisme)</term><term>Modèles moléculaires (MeSH)</term><term>Résonance magnétique nucléaire biomoléculaire (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Cysteine</term><term>Glutaredoxins</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cystéine</term><term>Glutarédoxines</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Biocatalysis</term><term>Kinetics</term><term>Models, Molecular</term><term>Nuclear Magnetic Resonance, Biomolecular</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Biocatalyse</term><term>Cinétique</term><term>Modèles moléculaires</term><term>Résonance magnétique nucléaire biomoléculaire</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The enzyme glutaredoxin catalyzes glutathione exchange, but little is known about its interaction with protein substrates. Very different proteins are substrates in vitro, and the enzyme seems to have low requirements for specific protein interactions. Here we present a systematic investigation of the interaction between human glutaredoxin 1 and glutathionylated variants of a single model protein. Thus, single cysteine variants of acyl-coenzyme A binding protein were produced creating a set of substrates in the same protein background. The rate constants for deglutathionylation differ by more than 2 orders of magnitude between the best (k1 = 1.75 × 10(5) M(-1) s(-1)) and the worst substrate (k1 = 4 × 10(2) M(-1) s(-1)). The pKa values of the substrate cysteine residues were determined by NMR spectroscopy and found to vary from 8.2 to 9.9. Rates of glutaredoxin 1-catalyzed deglutathionylation were assessed with respect to substrate cysteine pKa values, cysteine residue accessibility, local stability, and backbone dynamics. Good substrates are characterized by a combination of high accessibility of the glutathionylated site and low pKa of the cysteine residue. </div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">24673564</PMID><DateCompleted><Year>2014</Year><Month>06</Month><Day>09</Day></DateCompleted><DateRevised><Year>2014</Year><Month>04</Month><Day>23</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1520-4995</ISSN><JournalIssue CitedMedium="Internet"><Volume>53</Volume><Issue>15</Issue><PubDate><Year>2014</Year><Month>Apr</Month><Day>22</Day></PubDate></JournalIssue><Title>Biochemistry</Title><ISOAbbreviation>Biochemistry</ISOAbbreviation></Journal><ArticleTitle>The pKa value and accessibility of cysteine residues are key determinants for protein substrate discrimination by glutaredoxin.</ArticleTitle><Pagination><MedlinePgn>2533-40</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1021/bi4016633</ELocationID><Abstract><AbstractText>The enzyme glutaredoxin catalyzes glutathione exchange, but little is known about its interaction with protein substrates. Very different proteins are substrates in vitro, and the enzyme seems to have low requirements for specific protein interactions. Here we present a systematic investigation of the interaction between human glutaredoxin 1 and glutathionylated variants of a single model protein. Thus, single cysteine variants of acyl-coenzyme A binding protein were produced creating a set of substrates in the same protein background. The rate constants for deglutathionylation differ by more than 2 orders of magnitude between the best (k1 = 1.75 × 10(5) M(-1) s(-1)) and the worst substrate (k1 = 4 × 10(2) M(-1) s(-1)). The pKa values of the substrate cysteine residues were determined by NMR spectroscopy and found to vary from 8.2 to 9.9. Rates of glutaredoxin 1-catalyzed deglutathionylation were assessed with respect to substrate cysteine pKa values, cysteine residue accessibility, local stability, and backbone dynamics. Good substrates are characterized by a combination of high accessibility of the glutathionylated site and low pKa of the cysteine residue. </AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Jensen</LastName><ForeName>Kristine Steen</ForeName><Initials>KS</Initials><AffiliationInfo><Affiliation>Department of Biology, University of Copenhagen , Ole Maaleøs Vej 5, 2200 Copenhagen N, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pedersen</LastName><ForeName>Jeppe T</ForeName><Initials>JT</Initials></Author><Author ValidYN="Y"><LastName>Winther</LastName><ForeName>Jakob R</ForeName><Initials>JR</Initials></Author><Author ValidYN="Y"><LastName>Teilum</LastName><ForeName>Kaare</ForeName><Initials>K</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2014</Year><Month>04</Month><Day>09</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Biochemistry</MedlineTA><NlmUniqueID>0370623</NlmUniqueID><ISSNLinking>0006-2960</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D054477">Glutaredoxins</NameOfSubstance></Chemical><Chemical><RegistryNumber>K848JZ4886</RegistryNumber><NameOfSubstance UI="D003545">Cysteine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D055162" MajorTopicYN="N">Biocatalysis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D003545" MajorTopicYN="N">Cysteine</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D054477" MajorTopicYN="N">Glutaredoxins</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007700" MajorTopicYN="N">Kinetics</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008958" MajorTopicYN="N">Models, Molecular</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019906" MajorTopicYN="N">Nuclear Magnetic Resonance, Biomolecular</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2014</Year><Month>3</Month><Day>29</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2014</Year><Month>3</Month><Day>29</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2014</Year><Month>6</Month><Day>10</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">24673564</ArticleId><ArticleId IdType="doi">10.1021/bi4016633</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Danemark</li></country></list><tree><noCountry><name sortKey="Pedersen, Jeppe T" sort="Pedersen, Jeppe T" uniqKey="Pedersen J" first="Jeppe T" last="Pedersen">Jeppe T. Pedersen</name><name sortKey="Teilum, Kaare" sort="Teilum, Kaare" uniqKey="Teilum K" first="Kaare" last="Teilum">Kaare Teilum</name><name sortKey="Winther, Jakob R" sort="Winther, Jakob R" uniqKey="Winther J" first="Jakob R" last="Winther">Jakob R. Winther</name></noCountry><country name="Danemark"><noRegion><name sortKey="Jensen, Kristine Steen" sort="Jensen, Kristine Steen" uniqKey="Jensen K" first="Kristine Steen" last="Jensen">Kristine Steen Jensen</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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