Heparinoids activate a protease, secreted by mucosa and tumors, via tethering supplemented by allostery.
Identifieur interne : 001C41 ( Main/Curation ); précédent : 001C40; suivant : 001C42Heparinoids activate a protease, secreted by mucosa and tumors, via tethering supplemented by allostery.
Auteurs : Yan G. Fulcher [États-Unis] ; Raghavendar Reddy Sanganna Gari ; Nathan C. Frey ; Fuming Zhang ; Robert J. Linhardt ; Gavin M. King ; Steven R. Van DorenSource :
- ACS chemical biology [ 1554-8937 ] ; 2014.
Descripteurs français
- KwdFr :
- Activation enzymatique, Animaux, Humains, Héparinoïde (pharmacologie), Liaison aux protéines, Matrix metalloproteinase 7 (génétique), Matrix metalloproteinase 7 (métabolisme), Microscopie à force atomique, Modèles biologiques, Muqueuse (métabolisme), Peptide hydrolases (), Peptide hydrolases (métabolisme), Propriétés de surface, Rats, Régulation allostérique, Tumeurs (métabolisme).
- MESH :
- génétique : Matrix metalloproteinase 7.
- métabolisme : Matrix metalloproteinase 7, Muqueuse, Peptide hydrolases, Tumeurs.
- pharmacologie : Héparinoïde.
- Activation enzymatique, Animaux, Humains, Liaison aux protéines, Microscopie à force atomique, Modèles biologiques, Peptide hydrolases, Propriétés de surface, Rats, Régulation allostérique.
English descriptors
- KwdEn :
- Allosteric Regulation, Animals, Enzyme Activation, Heparinoids (pharmacology), Humans, Matrix Metalloproteinase 7 (genetics), Matrix Metalloproteinase 7 (metabolism), Microscopy, Atomic Force, Models, Biological, Mucous Membrane (metabolism), Neoplasms (metabolism), Peptide Hydrolases (drug effects), Peptide Hydrolases (metabolism), Protein Binding, Rats, Surface Properties.
- MESH :
- chemical , drug effects : Peptide Hydrolases.
- chemical , genetics : Matrix Metalloproteinase 7.
- chemical , metabolism : Matrix Metalloproteinase 7, Peptide Hydrolases.
- chemical , pharmacology : Heparinoids.
- metabolism : Mucous Membrane, Neoplasms.
- Allosteric Regulation, Animals, Enzyme Activation, Humans, Microscopy, Atomic Force, Models, Biological, Protein Binding, Rats, Surface Properties.
Abstract
Activation by glycosaminoglycans (GAGs) is an emerging trend among extracellular proteases important in disease. ProMMP-7, the zymogen of a matrix metalloproteinase secreted by mucosal epithelial and tumor cells, is activated at their surfaces by sulfated GAGs, but how? ProMMP-7 is activated in trans by representative heparin oligosaccharides in a length-dependent manner, with a large jump in activation at lengths of 16 monosaccharides. Imaging by atomic force microscopy visualized small complexes of proMMP-7 molecules linked by 8-mer lengths of heparinoids and extended assembles formed with 16-mer lengths of heparin. Complexes of proMMP-7 with polydisperse heparin or heparan sulfate were more diverse. Heparinoids evidently accelerate activation by tethering multiple proMMP-7 molecules together for proteolytic attack among neighbors. Removal of either the prodomain or C-terminal peptide sequence of KRSNSRKK from MMP-7 prevents formation of the long arrays induced by heparin 16-mers or heparan sulfate. The role of the C-terminus in activation assays suggests it contributes to remote, allosteric binding of GAGs. Enhancement of proteolytic velocity of MMP-by GAGs indicates them to be effectors of V-type allostery. GAGs from proteoglycans appear to assemble proMMP-7 molecules for activation, an event preceding its tumorigenic or antibacterial proteolytic activities at cell surfaces.
DOI: 10.1021/cb400898t
PubMed: 24495220
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: Pour aller vers cette notice dans l'étape Curation :001A65
- to stream PubMed, to step Curation: Pour aller vers cette notice dans l'étape Curation :001A65
- to stream PubMed, to step Checkpoint: Pour aller vers cette notice dans l'étape Curation :001893
- to stream Ncbi, to step Merge: Pour aller vers cette notice dans l'étape Curation :000C78
- to stream Ncbi, to step Curation: Pour aller vers cette notice dans l'étape Curation :000C78
- to stream Ncbi, to step Checkpoint: Pour aller vers cette notice dans l'étape Curation :000C78
- to stream Main, to step Merge: Pour aller vers cette notice dans l'étape Curation :001C54
Links to Exploration step
pubmed:24495220Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Heparinoids activate a protease, secreted by mucosa and tumors, via tethering supplemented by allostery.</title><author><name sortKey="Fulcher, Yan G" sort="Fulcher, Yan G" uniqKey="Fulcher Y" first="Yan G" last="Fulcher">Yan G. Fulcher</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry and ‡Department of Physics and Astronomy, University of Missouri , Columbia, Missouri 65211, United States.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biochemistry and ‡Department of Physics and Astronomy, University of Missouri , Columbia, Missouri 65211</wicri:regionArea><wicri:noRegion>Missouri 65211</wicri:noRegion></affiliation></author><author><name sortKey="Sanganna Gari, Raghavendar Reddy" sort="Sanganna Gari, Raghavendar Reddy" uniqKey="Sanganna Gari R" first="Raghavendar Reddy" last="Sanganna Gari">Raghavendar Reddy Sanganna Gari</name></author><author><name sortKey="Frey, Nathan C" sort="Frey, Nathan C" uniqKey="Frey N" first="Nathan C" last="Frey">Nathan C. Frey</name></author><author><name sortKey="Zhang, Fuming" sort="Zhang, Fuming" uniqKey="Zhang F" first="Fuming" last="Zhang">Fuming Zhang</name></author><author><name sortKey="Linhardt, Robert J" sort="Linhardt, Robert J" uniqKey="Linhardt R" first="Robert J" last="Linhardt">Robert J. Linhardt</name></author><author><name sortKey="King, Gavin M" sort="King, Gavin M" uniqKey="King G" first="Gavin M" last="King">Gavin M. King</name></author><author><name sortKey="Van Doren, Steven R" sort="Van Doren, Steven R" uniqKey="Van Doren S" first="Steven R" last="Van Doren">Steven R. Van Doren</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:24495220</idno><idno type="pmid">24495220</idno><idno type="doi">10.1021/cb400898t</idno><idno type="wicri:Area/PubMed/Corpus">001A65</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001A65</idno><idno type="wicri:Area/PubMed/Curation">001A65</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001A65</idno><idno type="wicri:Area/PubMed/Checkpoint">001893</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001893</idno><idno type="wicri:Area/Ncbi/Merge">000C78</idno><idno type="wicri:Area/Ncbi/Curation">000C78</idno><idno type="wicri:Area/Ncbi/Checkpoint">000C78</idno><idno type="wicri:Area/Main/Merge">001C54</idno><idno type="wicri:Area/Main/Curation">001C41</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Heparinoids activate a protease, secreted by mucosa and tumors, via tethering supplemented by allostery.</title><author><name sortKey="Fulcher, Yan G" sort="Fulcher, Yan G" uniqKey="Fulcher Y" first="Yan G" last="Fulcher">Yan G. Fulcher</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry and ‡Department of Physics and Astronomy, University of Missouri , Columbia, Missouri 65211, United States.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Biochemistry and ‡Department of Physics and Astronomy, University of Missouri , Columbia, Missouri 65211</wicri:regionArea><wicri:noRegion>Missouri 65211</wicri:noRegion></affiliation></author><author><name sortKey="Sanganna Gari, Raghavendar Reddy" sort="Sanganna Gari, Raghavendar Reddy" uniqKey="Sanganna Gari R" first="Raghavendar Reddy" last="Sanganna Gari">Raghavendar Reddy Sanganna Gari</name></author><author><name sortKey="Frey, Nathan C" sort="Frey, Nathan C" uniqKey="Frey N" first="Nathan C" last="Frey">Nathan C. Frey</name></author><author><name sortKey="Zhang, Fuming" sort="Zhang, Fuming" uniqKey="Zhang F" first="Fuming" last="Zhang">Fuming Zhang</name></author><author><name sortKey="Linhardt, Robert J" sort="Linhardt, Robert J" uniqKey="Linhardt R" first="Robert J" last="Linhardt">Robert J. Linhardt</name></author><author><name sortKey="King, Gavin M" sort="King, Gavin M" uniqKey="King G" first="Gavin M" last="King">Gavin M. King</name></author><author><name sortKey="Van Doren, Steven R" sort="Van Doren, Steven R" uniqKey="Van Doren S" first="Steven R" last="Van Doren">Steven R. Van Doren</name></author></analytic><series><title level="j">ACS chemical biology</title><idno type="eISSN">1554-8937</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Allosteric Regulation</term><term>Animals</term><term>Enzyme Activation</term><term>Heparinoids (pharmacology)</term><term>Humans</term><term>Matrix Metalloproteinase 7 (genetics)</term><term>Matrix Metalloproteinase 7 (metabolism)</term><term>Microscopy, Atomic Force</term><term>Models, Biological</term><term>Mucous Membrane (metabolism)</term><term>Neoplasms (metabolism)</term><term>Peptide Hydrolases (drug effects)</term><term>Peptide Hydrolases (metabolism)</term><term>Protein Binding</term><term>Rats</term><term>Surface Properties</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Activation enzymatique</term><term>Animaux</term><term>Humains</term><term>Héparinoïde (pharmacologie)</term><term>Liaison aux protéines</term><term>Matrix metalloproteinase 7 (génétique)</term><term>Matrix metalloproteinase 7 (métabolisme)</term><term>Microscopie à force atomique</term><term>Modèles biologiques</term><term>Muqueuse (métabolisme)</term><term>Peptide hydrolases ()</term><term>Peptide hydrolases (métabolisme)</term><term>Propriétés de surface</term><term>Rats</term><term>Régulation allostérique</term><term>Tumeurs (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="drug effects" xml:lang="en"><term>Peptide Hydrolases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Matrix Metalloproteinase 7</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Matrix Metalloproteinase 7</term><term>Peptide Hydrolases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Heparinoids</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Matrix metalloproteinase 7</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Mucous Membrane</term><term>Neoplasms</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Matrix metalloproteinase 7</term><term>Muqueuse</term><term>Peptide hydrolases</term><term>Tumeurs</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Héparinoïde</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Allosteric Regulation</term><term>Animals</term><term>Enzyme Activation</term><term>Humans</term><term>Microscopy, Atomic Force</term><term>Models, Biological</term><term>Protein Binding</term><term>Rats</term><term>Surface Properties</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Activation enzymatique</term><term>Animaux</term><term>Humains</term><term>Liaison aux protéines</term><term>Microscopie à force atomique</term><term>Modèles biologiques</term><term>Peptide hydrolases</term><term>Propriétés de surface</term><term>Rats</term><term>Régulation allostérique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Activation by glycosaminoglycans (GAGs) is an emerging trend among extracellular proteases important in disease. ProMMP-7, the zymogen of a matrix metalloproteinase secreted by mucosal epithelial and tumor cells, is activated at their surfaces by sulfated GAGs, but how? ProMMP-7 is activated in trans by representative heparin oligosaccharides in a length-dependent manner, with a large jump in activation at lengths of 16 monosaccharides. Imaging by atomic force microscopy visualized small complexes of proMMP-7 molecules linked by 8-mer lengths of heparinoids and extended assembles formed with 16-mer lengths of heparin. Complexes of proMMP-7 with polydisperse heparin or heparan sulfate were more diverse. Heparinoids evidently accelerate activation by tethering multiple proMMP-7 molecules together for proteolytic attack among neighbors. Removal of either the prodomain or C-terminal peptide sequence of KRSNSRKK from MMP-7 prevents formation of the long arrays induced by heparin 16-mers or heparan sulfate. The role of the C-terminus in activation assays suggests it contributes to remote, allosteric binding of GAGs. Enhancement of proteolytic velocity of MMP-by GAGs indicates them to be effectors of V-type allostery. GAGs from proteoglycans appear to assemble proMMP-7 molecules for activation, an event preceding its tumorigenic or antibacterial proteolytic activities at cell surfaces. </div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/MersV1/Data/Main/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001C41 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Curation/biblio.hfd -nk 001C41 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= MersV1
|flux= Main
|étape= Curation
|type= RBID
|clé= pubmed:24495220
|texte= Heparinoids activate a protease, secreted by mucosa and tumors, via tethering supplemented by allostery.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Curation/RBID.i -Sk "pubmed:24495220" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Curation/biblio.hfd \
| NlmPubMed2Wicri -a MersV1
| This area was generated with Dilib version V0.6.33. |  |