Analysis of the two steps in polypeptide chain initiation inhibited by pactamycin.
Identifieur interne : 002B18 ( PubMed/Corpus ); précédent : 002B17; suivant : 002B19Analysis of the two steps in polypeptide chain initiation inhibited by pactamycin.
Auteurs : L S Kappen ; I H GoldbergSource :
- Biochemistry [ 0006-2960 ] ; 1976.
English descriptors
- KwdEn :
- Animals, Antibiotics, Antineoplastic (pharmacology), Binding Sites, Hemolysis, Oligopeptides (biosynthesis), Pactamycin (pharmacology), Peptide Chain Initiation, Translational (drug effects), Polyribosomes (metabolism), RNA, Transfer (metabolism), Rabbits, Reticulocytes (drug effects), Reticulocytes (metabolism), Ribosomes (metabolism), Sparsomycin (pharmacology).
- MESH :
- chemical , biosynthesis : Oligopeptides.
- chemical , metabolism : RNA, Transfer.
- chemical , pharmacology : Antibiotics, Antineoplastic, Pactamycin, Sparsomycin.
- drug effects : Peptide Chain Initiation, Translational, Reticulocytes.
- metabolism : Polyribosomes, Reticulocytes, Ribosomes.
- Animals, Binding Sites, Hemolysis, Rabbits.
Abstract
Earlier work has shown that the inhibition by pactamycin (PM) of polypeptide chain initiation in reticulocyte extracts is associated with (1) a defect in the joining of the 60S subunit to the smaller initiation complex to form an 80S complex ("joining reaction") (Kappen, L. S., Suzuki, H., and Goldberg, I. H. (1973), Proc. Natl. Acad. Sci. U.S.A. 70, 22) and (2) a block after the synthesis of the initial dipeptide (Kappen, L. S., and Goldberg, I. H. (1973), Biochem. Biophys. Res. Commun. 54, 1083). The relative contributions of these two effects to the action of PM and their relationship to one another were evaluated in a system employing sparsomycin that permits both initiation at a certain number of initiation sites and limited oligopeptide formation without termination and release. The degree to which PM blocks the "joining reaction" and leads to the accumulation of 48S initiation complexes that either remain free or are bound to polysomes without the corresponding 60S subunit ("half-mers") was estimated by treatment of polysomes with RNase. Met-tRNAfMet binding factors are required to stabilize the RNase-generated 48S complexes. Under conditions where the initiation factor required for the "joining reaction" functions catalytically, presumably by cycling on and off initiation complexes, PM usually inhibits 80S complex formation 50-70%. Where "joining" is not limiting (presence of at least stoichiometric amounts of joining factor or high Mg2+ concentration) PM leads to the maximal accumulation of the initial dipeptide, Met-Val, in the P-site on the ribosome, indicating a block in a subsequent step in elongation. Binding studies with [3H]PM and the inability of PM to inhibit elongation of preformed Met-Val indicate that PM must interact with the ribosomes at an early stage of initiation. Taken together these data are compatible with the suggestion that PM does not interfere with the ribosomal "joining reaction" per se, but prevents the release and reuse of the joining factor, and in so doing blocks a step in elongation after formation of the initial dipeptide and its translocation to the P-site on the ribosome.
DOI: 10.1021/bi00649a013
PubMed: 1247535
Links to Exploration step
pubmed:1247535Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Analysis of the two steps in polypeptide chain initiation inhibited by pactamycin.</title><author><name sortKey="Kappen, L S" sort="Kappen, L S" uniqKey="Kappen L" first="L S" last="Kappen">L S Kappen</name></author><author><name sortKey="Goldberg, I H" sort="Goldberg, I H" uniqKey="Goldberg I" first="I H" last="Goldberg">I H Goldberg</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="1976">1976</date><idno type="RBID">pubmed:1247535</idno><idno type="pmid">1247535</idno><idno type="doi">10.1021/bi00649a013</idno><idno type="wicri:Area/PubMed/Corpus">002B18</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002B18</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Analysis of the two steps in polypeptide chain initiation inhibited by pactamycin.</title><author><name sortKey="Kappen, L S" sort="Kappen, L S" uniqKey="Kappen L" first="L S" last="Kappen">L S Kappen</name></author><author><name sortKey="Goldberg, I H" sort="Goldberg, I H" uniqKey="Goldberg I" first="I H" last="Goldberg">I H Goldberg</name></author></analytic><series><title level="j">Biochemistry</title><idno type="ISSN">0006-2960</idno><imprint><date when="1976" type="published">1976</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antibiotics, Antineoplastic (pharmacology)</term><term>Binding Sites</term><term>Hemolysis</term><term>Oligopeptides (biosynthesis)</term><term>Pactamycin (pharmacology)</term><term>Peptide Chain Initiation, Translational (drug effects)</term><term>Polyribosomes (metabolism)</term><term>RNA, Transfer (metabolism)</term><term>Rabbits</term><term>Reticulocytes (drug effects)</term><term>Reticulocytes (metabolism)</term><term>Ribosomes (metabolism)</term><term>Sparsomycin (pharmacology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Oligopeptides</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>RNA, Transfer</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antibiotics, Antineoplastic</term><term>Pactamycin</term><term>Sparsomycin</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Peptide Chain Initiation, Translational</term><term>Reticulocytes</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Polyribosomes</term><term>Reticulocytes</term><term>Ribosomes</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Binding Sites</term><term>Hemolysis</term><term>Rabbits</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Earlier work has shown that the inhibition by pactamycin (PM) of polypeptide chain initiation in reticulocyte extracts is associated with (1) a defect in the joining of the 60S subunit to the smaller initiation complex to form an 80S complex ("joining reaction") (Kappen, L. S., Suzuki, H., and Goldberg, I. H. (1973), Proc. Natl. Acad. Sci. U.S.A. 70, 22) and (2) a block after the synthesis of the initial dipeptide (Kappen, L. S., and Goldberg, I. H. (1973), Biochem. Biophys. Res. Commun. 54, 1083). The relative contributions of these two effects to the action of PM and their relationship to one another were evaluated in a system employing sparsomycin that permits both initiation at a certain number of initiation sites and limited oligopeptide formation without termination and release. The degree to which PM blocks the "joining reaction" and leads to the accumulation of 48S initiation complexes that either remain free or are bound to polysomes without the corresponding 60S subunit ("half-mers") was estimated by treatment of polysomes with RNase. Met-tRNAfMet binding factors are required to stabilize the RNase-generated 48S complexes. Under conditions where the initiation factor required for the "joining reaction" functions catalytically, presumably by cycling on and off initiation complexes, PM usually inhibits 80S complex formation 50-70%. Where "joining" is not limiting (presence of at least stoichiometric amounts of joining factor or high Mg2+ concentration) PM leads to the maximal accumulation of the initial dipeptide, Met-Val, in the P-site on the ribosome, indicating a block in a subsequent step in elongation. Binding studies with [3H]PM and the inability of PM to inhibit elongation of preformed Met-Val indicate that PM must interact with the ribosomes at an early stage of initiation. Taken together these data are compatible with the suggestion that PM does not interfere with the ribosomal "joining reaction" per se, but prevents the release and reuse of the joining factor, and in so doing blocks a step in elongation after formation of the initial dipeptide and its translocation to the P-site on the ribosome.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">1247535</PMID><DateCompleted><Year>1976</Year><Month>04</Month><Day>29</Day></DateCompleted><DateRevised><Year>2019</Year><Month>06</Month><Day>13</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0006-2960</ISSN><JournalIssue CitedMedium="Print"><Volume>15</Volume><Issue>4</Issue><PubDate><Year>1976</Year><Month>Feb</Month><Day>24</Day></PubDate></JournalIssue><Title>Biochemistry</Title><ISOAbbreviation>Biochemistry</ISOAbbreviation></Journal><ArticleTitle>Analysis of the two steps in polypeptide chain initiation inhibited by pactamycin.</ArticleTitle><Pagination><MedlinePgn>811-8</MedlinePgn></Pagination><Abstract><AbstractText>Earlier work has shown that the inhibition by pactamycin (PM) of polypeptide chain initiation in reticulocyte extracts is associated with (1) a defect in the joining of the 60S subunit to the smaller initiation complex to form an 80S complex ("joining reaction") (Kappen, L. S., Suzuki, H., and Goldberg, I. H. (1973), Proc. Natl. Acad. Sci. U.S.A. 70, 22) and (2) a block after the synthesis of the initial dipeptide (Kappen, L. S., and Goldberg, I. H. (1973), Biochem. Biophys. Res. Commun. 54, 1083). The relative contributions of these two effects to the action of PM and their relationship to one another were evaluated in a system employing sparsomycin that permits both initiation at a certain number of initiation sites and limited oligopeptide formation without termination and release. The degree to which PM blocks the "joining reaction" and leads to the accumulation of 48S initiation complexes that either remain free or are bound to polysomes without the corresponding 60S subunit ("half-mers") was estimated by treatment of polysomes with RNase. Met-tRNAfMet binding factors are required to stabilize the RNase-generated 48S complexes. Under conditions where the initiation factor required for the "joining reaction" functions catalytically, presumably by cycling on and off initiation complexes, PM usually inhibits 80S complex formation 50-70%. Where "joining" is not limiting (presence of at least stoichiometric amounts of joining factor or high Mg2+ concentration) PM leads to the maximal accumulation of the initial dipeptide, Met-Val, in the P-site on the ribosome, indicating a block in a subsequent step in elongation. Binding studies with [3H]PM and the inability of PM to inhibit elongation of preformed Met-Val indicate that PM must interact with the ribosomes at an early stage of initiation. Taken together these data are compatible with the suggestion that PM does not interfere with the ribosomal "joining reaction" per se, but prevents the release and reuse of the joining factor, and in so doing blocks a step in elongation after formation of the initial dipeptide and its translocation to the P-site on the ribosome.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Kappen</LastName><ForeName>L S</ForeName><Initials>LS</Initials></Author><Author ValidYN="Y"><LastName>Goldberg</LastName><ForeName>I H</ForeName><Initials>IH</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013487">Research Support, U.S. Gov't, P.H.S.</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Biochemistry</MedlineTA><NlmUniqueID>0370623</NlmUniqueID><ISSNLinking>0006-2960</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000903">Antibiotics, Antineoplastic</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D009842">Oligopeptides</NameOfSubstance></Chemical><Chemical><RegistryNumber>23668-11-3</RegistryNumber><NameOfSubstance UI="D010142">Pactamycin</NameOfSubstance></Chemical><Chemical><RegistryNumber>6C940P63E7</RegistryNumber><NameOfSubstance UI="D013033">Sparsomycin</NameOfSubstance></Chemical><Chemical><RegistryNumber>9014-25-9</RegistryNumber><NameOfSubstance UI="D012343">RNA, Transfer</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000903" MajorTopicYN="N">Antibiotics, Antineoplastic</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001665" MajorTopicYN="N">Binding Sites</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006461" MajorTopicYN="N">Hemolysis</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009842" MajorTopicYN="N">Oligopeptides</DescriptorName><QualifierName UI="Q000096" MajorTopicYN="N">biosynthesis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010142" MajorTopicYN="N">Pactamycin</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010442" MajorTopicYN="N">Peptide Chain Initiation, Translational</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011132" MajorTopicYN="N">Polyribosomes</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012343" MajorTopicYN="N">RNA, Transfer</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011817" MajorTopicYN="N">Rabbits</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012156" MajorTopicYN="N">Reticulocytes</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D012270" MajorTopicYN="N">Ribosomes</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013033" MajorTopicYN="N">Sparsomycin</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>1976</Year><Month>2</Month><Day>24</Day></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>1976</Year><Month>2</Month><Day>24</Day><Hour>0</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>1976</Year><Month>2</Month><Day>24</Day><Hour>0</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">1247535</ArticleId><ArticleId IdType="doi">10.1021/bi00649a013</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/MersV1/Data/PubMed/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002B18 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/PubMed/Corpus/biblio.hfd -nk 002B18 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= MersV1
|flux= PubMed
|étape= Corpus
|type= RBID
|clé= pubmed:1247535
|texte= Analysis of the two steps in polypeptide chain initiation inhibited by pactamycin.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/PubMed/Corpus/RBID.i -Sk "pubmed:1247535" \
| HfdSelect -Kh $EXPLOR_AREA/Data/PubMed/Corpus/biblio.hfd \
| NlmPubMed2Wicri -a MersV1
| This area was generated with Dilib version V0.6.33. |  |