A single dipeptide sequence modulates the redox properties of a whole enzyme family.
Identifieur interne : 001152 ( Main/Exploration ); précédent : 001151; suivant : 001153A single dipeptide sequence modulates the redox properties of a whole enzyme family.
Auteurs : M. Huber-Wunderlich [Suisse] ; R. GlockshuberSource :
- Folding & design [ 1359-0278 ] ; 1998.
Descripteurs français
- KwdFr :
- Dipeptides (MeSH), Glutarédoxines (MeSH), Mutagenèse dirigée (MeSH), Oxidoreductases (MeSH), Oxydoréduction (MeSH), Protein Disulfide-Isomerases (génétique), Protein Disulfide-Isomerases (métabolisme), Protéines (métabolisme), Spécificité du substrat (MeSH), Stabilité enzymatique (MeSH), Sulfur-sulfur bond isomerase (génétique), Sulfur-sulfur bond isomerase (métabolisme), Thiorédoxines (métabolisme).
- MESH :
- génétique : Protein Disulfide-Isomerases, Sulfur-sulfur bond isomerase.
- métabolisme : Protein Disulfide-Isomerases, Protéines, Sulfur-sulfur bond isomerase, Thiorédoxines.
- Dipeptides, Glutarédoxines, Mutagenèse dirigée, Oxidoreductases, Oxydoréduction, Spécificité du substrat, Stabilité enzymatique.
English descriptors
- KwdEn :
- Dipeptides (MeSH), Enzyme Stability (MeSH), Glutaredoxins (MeSH), Mutagenesis, Site-Directed (MeSH), Oxidation-Reduction (MeSH), Oxidoreductases (MeSH), Protein Disulfide-Isomerases (genetics), Protein Disulfide-Isomerases (metabolism), Proteins (metabolism), Substrate Specificity (MeSH), Sulfur-Sulfur Bond Isomerases (genetics), Sulfur-Sulfur Bond Isomerases (metabolism), Thioredoxins (metabolism).
- MESH :
- chemical , genetics : Protein Disulfide-Isomerases, Sulfur-Sulfur Bond Isomerases.
- chemical , metabolism : Protein Disulfide-Isomerases, Proteins, Sulfur-Sulfur Bond Isomerases, Thioredoxins.
- chemical : Dipeptides, Glutaredoxins, Oxidoreductases.
- Enzyme Stability, Mutagenesis, Site-Directed, Oxidation-Reduction, Substrate Specificity.
Abstract
BACKGROUND
Disulfide exchange reactions are catalyzed by thiol/disulfide oxidoreductases. These enzymes possess a thioredoxin fold and contain a catalytic disulfide with the sequence Cys-X-X-Cys at the N terminus of an alpha helix. Despite these similarities, the various members differ strongly in their redox potentials (-122 mV to -270 mV). Using the strong oxidant DsbA from Escherichia coli as a model system, we investigated whether the redox properties of these enzymes can be modulated rationally by exchange of the X-X dipeptide.
RESULTS
The X-X dipeptide of DsbA (Cys30-Pro31-His32-Cys33) was exchanged by the dipeptides of eukaryotic protein disulfide isomerase (PDI; Gly-His), glutaredoxin (Pro-Tyr), and thioredoxin (Gly-Pro) from E. coli. All variants were less oxidizing than wild-type DsbA and their redox potentials were in the order of the related natural enzymes (DsbA > PDI > glutaredoxin > thioredoxin). The equilibrium constant between glutathione and the thioredoxin-like variant increased 1200-fold compared with wild-type DsbA. The variants also showed a strong increase in the pKa of the nucleophilic cysteine (Cys30). As for glutaredoxin and thioredoxin, the catalytic disulfide stabilized the corresponding variants while destabilizing wild-type DsbA and the PDI-like variant.
CONCLUSIONS
The X-X dipeptide in the active site of thiol/disulfide oxidoreductases appears to be the main determinant of the redox properties of these enzymes. This empirical finding should be very useful for the design of new thiol/disulfide oxidoreductases with altered redox potentials and for studying the function of these enzymes in vivo.
DOI: 10.1016/S1359-0278(98)00024-8
PubMed: 9562546
Affiliations:
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Glockshuber</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="1998">1998</date><idno type="RBID">pubmed:9562546</idno><idno type="pmid">9562546</idno><idno type="doi">10.1016/S1359-0278(98)00024-8</idno><idno type="wicri:Area/Main/Corpus">001141</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">001141</idno><idno type="wicri:Area/Main/Curation">001141</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">001141</idno><idno type="wicri:Area/Main/Exploration">001141</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">A single dipeptide sequence modulates the redox properties of a whole enzyme family.</title><author><name sortKey="Huber Wunderlich, M" sort="Huber Wunderlich, M" uniqKey="Huber Wunderlich M" first="M" last="Huber-Wunderlich">M. Huber-Wunderlich</name><affiliation wicri:level="3"><nlm:affiliation>Institut für Molekularbiologie und Biophysik, Eidgenössische Technische Hochschule, Hönggerberg CH-8093, Zürich, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Institut für Molekularbiologie und Biophysik, Eidgenössische Technische Hochschule, Hönggerberg CH-8093, Zürich</wicri:regionArea><placeName><settlement type="city">Zurich</settlement><region nuts="3" type="region">Canton de Zurich</region></placeName></affiliation></author><author><name sortKey="Glockshuber, R" sort="Glockshuber, R" uniqKey="Glockshuber R" first="R" last="Glockshuber">R. Glockshuber</name></author></analytic><series><title level="j">Folding & design</title><idno type="ISSN">1359-0278</idno><imprint><date when="1998" type="published">1998</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Dipeptides (MeSH)</term><term>Enzyme Stability (MeSH)</term><term>Glutaredoxins (MeSH)</term><term>Mutagenesis, Site-Directed (MeSH)</term><term>Oxidation-Reduction (MeSH)</term><term>Oxidoreductases (MeSH)</term><term>Protein Disulfide-Isomerases (genetics)</term><term>Protein Disulfide-Isomerases (metabolism)</term><term>Proteins (metabolism)</term><term>Substrate Specificity (MeSH)</term><term>Sulfur-Sulfur Bond Isomerases (genetics)</term><term>Sulfur-Sulfur Bond Isomerases (metabolism)</term><term>Thioredoxins (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Dipeptides (MeSH)</term><term>Glutarédoxines (MeSH)</term><term>Mutagenèse dirigée (MeSH)</term><term>Oxidoreductases (MeSH)</term><term>Oxydoréduction (MeSH)</term><term>Protein Disulfide-Isomerases (génétique)</term><term>Protein Disulfide-Isomerases (métabolisme)</term><term>Protéines (métabolisme)</term><term>Spécificité du substrat (MeSH)</term><term>Stabilité enzymatique (MeSH)</term><term>Sulfur-sulfur bond isomerase (génétique)</term><term>Sulfur-sulfur bond isomerase (métabolisme)</term><term>Thiorédoxines (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Protein Disulfide-Isomerases</term><term>Sulfur-Sulfur Bond Isomerases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Protein Disulfide-Isomerases</term><term>Proteins</term><term>Sulfur-Sulfur Bond Isomerases</term><term>Thioredoxins</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Dipeptides</term><term>Glutaredoxins</term><term>Oxidoreductases</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Protein Disulfide-Isomerases</term><term>Sulfur-sulfur bond isomerase</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Protein Disulfide-Isomerases</term><term>Protéines</term><term>Sulfur-sulfur bond isomerase</term><term>Thiorédoxines</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Enzyme Stability</term><term>Mutagenesis, Site-Directed</term><term>Oxidation-Reduction</term><term>Substrate Specificity</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Dipeptides</term><term>Glutarédoxines</term><term>Mutagenèse dirigée</term><term>Oxidoreductases</term><term>Oxydoréduction</term><term>Spécificité du substrat</term><term>Stabilité enzymatique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>BACKGROUND</b></p><p>Disulfide exchange reactions are catalyzed by thiol/disulfide oxidoreductases. These enzymes possess a thioredoxin fold and contain a catalytic disulfide with the sequence Cys-X-X-Cys at the N terminus of an alpha helix. Despite these similarities, the various members differ strongly in their redox potentials (-122 mV to -270 mV). Using the strong oxidant DsbA from Escherichia coli as a model system, we investigated whether the redox properties of these enzymes can be modulated rationally by exchange of the X-X dipeptide.</p></div><div type="abstract" xml:lang="en"><p><b>RESULTS</b></p><p>The X-X dipeptide of DsbA (Cys30-Pro31-His32-Cys33) was exchanged by the dipeptides of eukaryotic protein disulfide isomerase (PDI; Gly-His), glutaredoxin (Pro-Tyr), and thioredoxin (Gly-Pro) from E. coli. All variants were less oxidizing than wild-type DsbA and their redox potentials were in the order of the related natural enzymes (DsbA > PDI > glutaredoxin > thioredoxin). The equilibrium constant between glutathione and the thioredoxin-like variant increased 1200-fold compared with wild-type DsbA. The variants also showed a strong increase in the pKa of the nucleophilic cysteine (Cys30). As for glutaredoxin and thioredoxin, the catalytic disulfide stabilized the corresponding variants while destabilizing wild-type DsbA and the PDI-like variant.</p></div><div type="abstract" xml:lang="en"><p><b>CONCLUSIONS</b></p><p>The X-X dipeptide in the active site of thiol/disulfide oxidoreductases appears to be the main determinant of the redox properties of these enzymes. This empirical finding should be very useful for the design of new thiol/disulfide oxidoreductases with altered redox potentials and for studying the function of these enzymes in vivo.</p></div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">9562546</PMID><DateCompleted><Year>1998</Year><Month>07</Month><Day>10</Day></DateCompleted><DateRevised><Year>2008</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">1359-0278</ISSN><JournalIssue CitedMedium="Print"><Volume>3</Volume><Issue>3</Issue><PubDate><Year>1998</Year></PubDate></JournalIssue><Title>Folding & design</Title><ISOAbbreviation>Fold Des</ISOAbbreviation></Journal><ArticleTitle>A single dipeptide sequence modulates the redox properties of a whole enzyme family.</ArticleTitle><Pagination><MedlinePgn>161-71</MedlinePgn></Pagination><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Disulfide exchange reactions are catalyzed by thiol/disulfide oxidoreductases. These enzymes possess a thioredoxin fold and contain a catalytic disulfide with the sequence Cys-X-X-Cys at the N terminus of an alpha helix. Despite these similarities, the various members differ strongly in their redox potentials (-122 mV to -270 mV). Using the strong oxidant DsbA from Escherichia coli as a model system, we investigated whether the redox properties of these enzymes can be modulated rationally by exchange of the X-X dipeptide.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">The X-X dipeptide of DsbA (Cys30-Pro31-His32-Cys33) was exchanged by the dipeptides of eukaryotic protein disulfide isomerase (PDI; Gly-His), glutaredoxin (Pro-Tyr), and thioredoxin (Gly-Pro) from E. coli. All variants were less oxidizing than wild-type DsbA and their redox potentials were in the order of the related natural enzymes (DsbA > PDI > glutaredoxin > thioredoxin). The equilibrium constant between glutathione and the thioredoxin-like variant increased 1200-fold compared with wild-type DsbA. The variants also showed a strong increase in the pKa of the nucleophilic cysteine (Cys30). As for glutaredoxin and thioredoxin, the catalytic disulfide stabilized the corresponding variants while destabilizing wild-type DsbA and the PDI-like variant.</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">The X-X dipeptide in the active site of thiol/disulfide oxidoreductases appears to be the main determinant of the redox properties of these enzymes. This empirical finding should be very useful for the design of new thiol/disulfide oxidoreductases with altered redox potentials and for studying the function of these enzymes in vivo.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Huber-Wunderlich</LastName><ForeName>M</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Institut für Molekularbiologie und Biophysik, Eidgenössische Technische Hochschule, Hönggerberg CH-8093, Zürich, Switzerland.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Glockshuber</LastName><ForeName>R</ForeName><Initials>R</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D003160">Comparative Study</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Fold Des</MedlineTA><NlmUniqueID>9604387</NlmUniqueID><ISSNLinking>1359-0278</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D004151">Dipeptides</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D054477">Glutaredoxins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011506">Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>52500-60-4</RegistryNumber><NameOfSubstance UI="D013879">Thioredoxins</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 1.-</RegistryNumber><NameOfSubstance UI="D010088">Oxidoreductases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 5.3.4.-</RegistryNumber><NameOfSubstance UI="D019749">Sulfur-Sulfur Bond Isomerases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 5.3.4.1</RegistryNumber><NameOfSubstance UI="D019704">Protein Disulfide-Isomerases</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D004151" MajorTopicYN="Y">Dipeptides</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004795" MajorTopicYN="N">Enzyme Stability</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D054477" MajorTopicYN="N">Glutaredoxins</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016297" MajorTopicYN="N">Mutagenesis, Site-Directed</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010084" MajorTopicYN="N">Oxidation-Reduction</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010088" MajorTopicYN="Y">Oxidoreductases</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019704" MajorTopicYN="N">Protein Disulfide-Isomerases</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011506" MajorTopicYN="N">Proteins</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013379" MajorTopicYN="N">Substrate Specificity</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019749" MajorTopicYN="N">Sulfur-Sulfur Bond Isomerases</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013879" MajorTopicYN="N">Thioredoxins</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>1998</Year><Month>6</Month><Day>18</Day></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>1998</Year><Month>6</Month><Day>18</Day><Hour>0</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>1998</Year><Month>6</Month><Day>18</Day><Hour>0</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">9562546</ArticleId><ArticleId IdType="pii">S1359-0278(98)00024-8</ArticleId><ArticleId IdType="doi">10.1016/S1359-0278(98)00024-8</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Suisse</li></country><region><li>Canton de Zurich</li></region><settlement><li>Zurich</li></settlement></list><tree><noCountry><name sortKey="Glockshuber, R" sort="Glockshuber, R" uniqKey="Glockshuber R" first="R" last="Glockshuber">R. Glockshuber</name></noCountry><country name="Suisse"><region name="Canton de Zurich"><name sortKey="Huber Wunderlich, M" sort="Huber Wunderlich, M" uniqKey="Huber Wunderlich M" first="M" last="Huber-Wunderlich">M. Huber-Wunderlich</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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