Structural insights into heparanase activity using a fluorogenic heparan sulfate disaccharide
A synthetic heparan sulfate disaccharide has been assessed as a fluorogenic heparanase substrate, enabling enzyme turnover and inhibition kinetics measurements despite slow turnover. Crystal structures with human heparanase also provide the first ever observation of a substrate in an activated 1 S 3...
Gespeichert in:
| Veröffentlicht in: | Chemical communications (Cambridge, England) England), 2020-11, Vol.56 (89), p.1378-13783 |
|---|---|
| Hauptverfasser: | , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 13783 |
|---|---|
| container_issue | 89 |
| container_start_page | 1378 |
| container_title | Chemical communications (Cambridge, England) |
| container_volume | 56 |
| creator | Wu, Liang Wimmer, Norbert Davies, Gideon J Ferro, Vito |
| description | A synthetic heparan sulfate disaccharide has been assessed as a fluorogenic heparanase substrate, enabling enzyme turnover and inhibition kinetics measurements despite slow turnover. Crystal structures with human heparanase also provide the first ever observation of a substrate in an activated
1
S
3
conformation, highlighting previously unknown interactions involved in enzymatic processing. Our data provide insights into the heparanase catalytic mechanism, and will inform the design of improved heparanase substrates and inhibitors.
Crystal structures with human heparanase provide the first ever observation of a substrate in an activated
1
S
3
conformation. |
| doi_str_mv | 10.1039/d0cc05932c |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_2452096565</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2458974566</sourcerecordid><originalsourceid>FETCH-LOGICAL-c337t-e8e5bc822ea7b5219d237d4fdfcdeffbe57eaa27e7ee48c2e5ab4f766e333f383</originalsourceid><addsrcrecordid>eNpd0UtLxDAQB_AgiruuXrwrAS8iVNOkadqj1CcseFDBi5Q0nexm6bZrHsJ-e7vuQzCXGZgfw_APQqcxuY4Jy29qohThOaNqDw1jliYRT7KP_VXP80iwhA_QkXMz0r-YZ4dowBgRjAo-RJ-v3gblg5UNNq0zk6l3feM7PIWFtLKVDrBU3nwbv8TBmXaCJdZN6Gw3gdaorcMuNFp6wLVxUqmptKaGY3SgZePgZFNH6P3h_q14isYvj8_F7ThSjAkfQQa8UhmlIEXFaZzXlIk60bVWNWhdARcgJRUgAJJMUeCySrRIU2CMaZaxEbpc713Y7iuA8-XcOAVNI1vogitpwinJU57ynl78o7Mu2La_bqWyXCQ8TXt1tVbKds5Z0OXCmrm0yzIm5Sr08o4UxW_oRY_PNytDNYd6R7cp9-BsDaxTu-nfr7EfkEmInw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2458974566</pqid></control><display><type>article</type><title>Structural insights into heparanase activity using a fluorogenic heparan sulfate disaccharide</title><source>MEDLINE</source><source>Royal Society Of Chemistry Journals 2008-</source><source>Alma/SFX Local Collection</source><creator>Wu, Liang ; Wimmer, Norbert ; Davies, Gideon J ; Ferro, Vito</creator><creatorcontrib>Wu, Liang ; Wimmer, Norbert ; Davies, Gideon J ; Ferro, Vito</creatorcontrib><description>A synthetic heparan sulfate disaccharide has been assessed as a fluorogenic heparanase substrate, enabling enzyme turnover and inhibition kinetics measurements despite slow turnover. Crystal structures with human heparanase also provide the first ever observation of a substrate in an activated
1
S
3
conformation, highlighting previously unknown interactions involved in enzymatic processing. Our data provide insights into the heparanase catalytic mechanism, and will inform the design of improved heparanase substrates and inhibitors.
Crystal structures with human heparanase provide the first ever observation of a substrate in an activated
1
S
3
conformation.</description><identifier>ISSN: 1359-7345</identifier><identifier>EISSN: 1364-548X</identifier><identifier>DOI: 10.1039/d0cc05932c</identifier><identifier>PMID: 33073275</identifier><language>eng</language><publisher>England: Royal Society of Chemistry</publisher><subject>Catalysis ; Crystal structure ; Crystallography, X-Ray ; Disaccharides ; Disaccharides - chemistry ; Glucuronidase - chemistry ; Heparan sulfate ; Heparitin Sulfate - chemistry ; Humans ; Magnetic Resonance Spectroscopy ; NMR ; Nuclear magnetic resonance ; Protein Conformation ; Spectrometry, Mass, Electrospray Ionization ; Substrate inhibition ; Substrate Specificity</subject><ispartof>Chemical communications (Cambridge, England), 2020-11, Vol.56 (89), p.1378-13783</ispartof><rights>Copyright Royal Society of Chemistry 2020</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c337t-e8e5bc822ea7b5219d237d4fdfcdeffbe57eaa27e7ee48c2e5ab4f766e333f383</citedby><cites>FETCH-LOGICAL-c337t-e8e5bc822ea7b5219d237d4fdfcdeffbe57eaa27e7ee48c2e5ab4f766e333f383</cites><orcidid>0000-0003-3306-2550 ; 0000-0002-7343-776X ; 0000-0003-0294-7065</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33073275$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Liang</creatorcontrib><creatorcontrib>Wimmer, Norbert</creatorcontrib><creatorcontrib>Davies, Gideon J</creatorcontrib><creatorcontrib>Ferro, Vito</creatorcontrib><title>Structural insights into heparanase activity using a fluorogenic heparan sulfate disaccharide</title><title>Chemical communications (Cambridge, England)</title><addtitle>Chem Commun (Camb)</addtitle><description>A synthetic heparan sulfate disaccharide has been assessed as a fluorogenic heparanase substrate, enabling enzyme turnover and inhibition kinetics measurements despite slow turnover. Crystal structures with human heparanase also provide the first ever observation of a substrate in an activated
1
S
3
conformation, highlighting previously unknown interactions involved in enzymatic processing. Our data provide insights into the heparanase catalytic mechanism, and will inform the design of improved heparanase substrates and inhibitors.
Crystal structures with human heparanase provide the first ever observation of a substrate in an activated
1
S
3
conformation.</description><subject>Catalysis</subject><subject>Crystal structure</subject><subject>Crystallography, X-Ray</subject><subject>Disaccharides</subject><subject>Disaccharides - chemistry</subject><subject>Glucuronidase - chemistry</subject><subject>Heparan sulfate</subject><subject>Heparitin Sulfate - chemistry</subject><subject>Humans</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>NMR</subject><subject>Nuclear magnetic resonance</subject><subject>Protein Conformation</subject><subject>Spectrometry, Mass, Electrospray Ionization</subject><subject>Substrate inhibition</subject><subject>Substrate Specificity</subject><issn>1359-7345</issn><issn>1364-548X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpd0UtLxDAQB_AgiruuXrwrAS8iVNOkadqj1CcseFDBi5Q0nexm6bZrHsJ-e7vuQzCXGZgfw_APQqcxuY4Jy29qohThOaNqDw1jliYRT7KP_VXP80iwhA_QkXMz0r-YZ4dowBgRjAo-RJ-v3gblg5UNNq0zk6l3feM7PIWFtLKVDrBU3nwbv8TBmXaCJdZN6Gw3gdaorcMuNFp6wLVxUqmptKaGY3SgZePgZFNH6P3h_q14isYvj8_F7ThSjAkfQQa8UhmlIEXFaZzXlIk60bVWNWhdARcgJRUgAJJMUeCySrRIU2CMaZaxEbpc713Y7iuA8-XcOAVNI1vogitpwinJU57ynl78o7Mu2La_bqWyXCQ8TXt1tVbKds5Z0OXCmrm0yzIm5Sr08o4UxW_oRY_PNytDNYd6R7cp9-BsDaxTu-nfr7EfkEmInw</recordid><startdate>20201110</startdate><enddate>20201110</enddate><creator>Wu, Liang</creator><creator>Wimmer, Norbert</creator><creator>Davies, Gideon J</creator><creator>Ferro, Vito</creator><general>Royal Society of Chemistry</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7SR</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>L7M</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-3306-2550</orcidid><orcidid>https://orcid.org/0000-0002-7343-776X</orcidid><orcidid>https://orcid.org/0000-0003-0294-7065</orcidid></search><sort><creationdate>20201110</creationdate><title>Structural insights into heparanase activity using a fluorogenic heparan sulfate disaccharide</title><author>Wu, Liang ; Wimmer, Norbert ; Davies, Gideon J ; Ferro, Vito</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c337t-e8e5bc822ea7b5219d237d4fdfcdeffbe57eaa27e7ee48c2e5ab4f766e333f383</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Catalysis</topic><topic>Crystal structure</topic><topic>Crystallography, X-Ray</topic><topic>Disaccharides</topic><topic>Disaccharides - chemistry</topic><topic>Glucuronidase - chemistry</topic><topic>Heparan sulfate</topic><topic>Heparitin Sulfate - chemistry</topic><topic>Humans</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>NMR</topic><topic>Nuclear magnetic resonance</topic><topic>Protein Conformation</topic><topic>Spectrometry, Mass, Electrospray Ionization</topic><topic>Substrate inhibition</topic><topic>Substrate Specificity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Liang</creatorcontrib><creatorcontrib>Wimmer, Norbert</creatorcontrib><creatorcontrib>Davies, Gideon J</creatorcontrib><creatorcontrib>Ferro, Vito</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>MEDLINE - Academic</collection><jtitle>Chemical communications (Cambridge, England)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Liang</au><au>Wimmer, Norbert</au><au>Davies, Gideon J</au><au>Ferro, Vito</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Structural insights into heparanase activity using a fluorogenic heparan sulfate disaccharide</atitle><jtitle>Chemical communications (Cambridge, England)</jtitle><addtitle>Chem Commun (Camb)</addtitle><date>2020-11-10</date><risdate>2020</risdate><volume>56</volume><issue>89</issue><spage>1378</spage><epage>13783</epage><pages>1378-13783</pages><issn>1359-7345</issn><eissn>1364-548X</eissn><abstract>A synthetic heparan sulfate disaccharide has been assessed as a fluorogenic heparanase substrate, enabling enzyme turnover and inhibition kinetics measurements despite slow turnover. Crystal structures with human heparanase also provide the first ever observation of a substrate in an activated
1
S
3
conformation, highlighting previously unknown interactions involved in enzymatic processing. Our data provide insights into the heparanase catalytic mechanism, and will inform the design of improved heparanase substrates and inhibitors.
Crystal structures with human heparanase provide the first ever observation of a substrate in an activated
1
S
3
conformation.</abstract><cop>England</cop><pub>Royal Society of Chemistry</pub><pmid>33073275</pmid><doi>10.1039/d0cc05932c</doi><tpages>4</tpages><orcidid>https://orcid.org/0000-0003-3306-2550</orcidid><orcidid>https://orcid.org/0000-0002-7343-776X</orcidid><orcidid>https://orcid.org/0000-0003-0294-7065</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1359-7345 |
| ispartof | Chemical communications (Cambridge, England), 2020-11, Vol.56 (89), p.1378-13783 |
| issn | 1359-7345 1364-548X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2452096565 |
| source | MEDLINE; Royal Society Of Chemistry Journals 2008-; Alma/SFX Local Collection |
| subjects | Catalysis Crystal structure Crystallography, X-Ray Disaccharides Disaccharides - chemistry Glucuronidase - chemistry Heparan sulfate Heparitin Sulfate - chemistry Humans Magnetic Resonance Spectroscopy NMR Nuclear magnetic resonance Protein Conformation Spectrometry, Mass, Electrospray Ionization Substrate inhibition Substrate Specificity |
| title | Structural insights into heparanase activity using a fluorogenic heparan sulfate disaccharide |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T01%3A43%3A41IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Structural%20insights%20into%20heparanase%20activity%20using%20a%20fluorogenic%20heparan%20sulfate%20disaccharide&rft.jtitle=Chemical%20communications%20(Cambridge,%20England)&rft.au=Wu,%20Liang&rft.date=2020-11-10&rft.volume=56&rft.issue=89&rft.spage=1378&rft.epage=13783&rft.pages=1378-13783&rft.issn=1359-7345&rft.eissn=1364-548X&rft_id=info:doi/10.1039/d0cc05932c&rft_dat=%3Cproquest_pubme%3E2458974566%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2458974566&rft_id=info:pmid/33073275&rfr_iscdi=true |