Crystal structures of human pancreatic alpha-amylase in complex with carbohydrate and proteinaceous inhibitors
Crystal structures of human pancreatic alpha-amylase (HPA) in complex with naturally occurring inhibitors have been solved. The tetrasaccharide acarbose and a pseudo-pentasaccharide of the trestatin family produced identical continuous electron densities corresponding to a pentasaccharide species, s...
Gespeichert in:
| Veröffentlicht in: | Biochemical journal 2000-02, Vol.346 Pt 1 (1), p.201-208 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 208 |
|---|---|
| container_issue | 1 |
| container_start_page | 201 |
| container_title | Biochemical journal |
| container_volume | 346 Pt 1 |
| creator | Nahoum, V Roux, G Anton, V Rougé, P Puigserver, A Bischoff, H Henrissat, B Payan, F |
| description | Crystal structures of human pancreatic alpha-amylase (HPA) in complex with naturally occurring inhibitors have been solved. The tetrasaccharide acarbose and a pseudo-pentasaccharide of the trestatin family produced identical continuous electron densities corresponding to a pentasaccharide species, spanning the -3 to +2 subsites of the enzyme, presumably resulting from transglycosylation. Binding of the acarviosine core linked to a glucose residue at subsites -1 to +2 appears to be a critical part of the interaction process between alpha-amylases and trestatin-derived inhibitors. Two crystal forms, obtained at different values of pH, for the complex of HPA with the protein inhibitor from Phaseolus vulgaris (alpha-amylase inhibitor) have been solved. The flexible loop typical of the mammalian alpha-amylases was shown to exist in two different conformations, suggesting that loop closure is pH-sensitive. Structural information is provided for the important inhibitor residue, Arg-74, which has not been observed previously in structural analyses. |
| doi_str_mv | 10.1042/0264-6021:3460201 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1220841</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>70882068</sourcerecordid><originalsourceid>FETCH-LOGICAL-c429t-2fcb15183944e2932e3387395b84795b145d8738d3e50be29adb5ce593fe4b303</originalsourceid><addsrcrecordid>eNpdkU-L1EAQxRtR3HH1A3iRPgkeotV_Mul4EJZBXWHAi56bSqdiWpJ07O6szrc3YYZl9VJFdf3ea4rH2EsBbwVo-Q7kXhd7kOK90msD8YjthK6gMJU0j9nufn_FnqX0E0Bo0PCUXQnYl5UszY5Nh3hKGQeeclxcXiIlHjreLyNOfMbJRcLsHcdh7rHA8TRgIu4n7sI4D_SH__a55w5jE_pTGzETx6nlcwyZ_ISOwpJWvPeNzyGm5-xJh0OiF5d-zb5_-vjtcFscv37-crg5Fk7LOheyc40ohVG11iRrJUkpU6m6bIyu1ip02a6zaRWV0KwEtk3pqKxVR7pRoK7Zh7PvvDQjtY6mHHGwc_QjxpMN6O2_m8n39ke4s0JKMFqsBm_OBv1_stubo93eQBhdSwV3G_v68lkMvxZK2Y4-ORoGnLbzbQXGSNibFRRn0MWQUqTu3lmA3RK1W2J2S8xeEl01rx5e8kBxjlD9BVVrnb0</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>70882068</pqid></control><display><type>article</type><title>Crystal structures of human pancreatic alpha-amylase in complex with carbohydrate and proteinaceous inhibitors</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Nahoum, V ; Roux, G ; Anton, V ; Rougé, P ; Puigserver, A ; Bischoff, H ; Henrissat, B ; Payan, F</creator><creatorcontrib>Nahoum, V ; Roux, G ; Anton, V ; Rougé, P ; Puigserver, A ; Bischoff, H ; Henrissat, B ; Payan, F</creatorcontrib><description>Crystal structures of human pancreatic alpha-amylase (HPA) in complex with naturally occurring inhibitors have been solved. The tetrasaccharide acarbose and a pseudo-pentasaccharide of the trestatin family produced identical continuous electron densities corresponding to a pentasaccharide species, spanning the -3 to +2 subsites of the enzyme, presumably resulting from transglycosylation. Binding of the acarviosine core linked to a glucose residue at subsites -1 to +2 appears to be a critical part of the interaction process between alpha-amylases and trestatin-derived inhibitors. Two crystal forms, obtained at different values of pH, for the complex of HPA with the protein inhibitor from Phaseolus vulgaris (alpha-amylase inhibitor) have been solved. The flexible loop typical of the mammalian alpha-amylases was shown to exist in two different conformations, suggesting that loop closure is pH-sensitive. Structural information is provided for the important inhibitor residue, Arg-74, which has not been observed previously in structural analyses.</description><identifier>ISSN: 0264-6021</identifier><identifier>EISSN: 1470-8728</identifier><identifier>DOI: 10.1042/0264-6021:3460201</identifier><identifier>PMID: 10657258</identifier><language>eng</language><publisher>England: Portland Press</publisher><subject>Acarbose - chemistry ; Acarbose - metabolism ; Acarbose - pharmacology ; alpha-Amylases - antagonists & inhibitors ; alpha-Amylases - chemistry ; alpha-Amylases - metabolism ; Amino Sugars - metabolism ; Amino Sugars - pharmacology ; Arginine - chemistry ; Arginine - metabolism ; Binding Sites ; Biochemistry, Molecular Biology ; Crystallography, X-Ray ; Electrons ; Enzyme Inhibitors - chemistry ; Enzyme Inhibitors - metabolism ; Enzyme Inhibitors - pharmacology ; Glycosylation ; Humans ; Hydrogen Bonding ; Hydrogen-Ion Concentration ; Lectins - chemistry ; Lectins - metabolism ; Lectins - pharmacology ; Life Sciences ; Models, Molecular ; Molecular Sequence Data ; Pancreas - enzymology ; Plant Lectins ; Plant Proteins - chemistry ; Plant Proteins - metabolism ; Plant Proteins - pharmacology ; Polysaccharides - chemistry ; Polysaccharides - metabolism ; Polysaccharides - pharmacology ; Protein Conformation ; Structural Biology ; Trisaccharides - chemistry ; Trisaccharides - metabolism ; Trisaccharides - pharmacology</subject><ispartof>Biochemical journal, 2000-02, Vol.346 Pt 1 (1), p.201-208</ispartof><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c429t-2fcb15183944e2932e3387395b84795b145d8738d3e50be29adb5ce593fe4b303</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1220841/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1220841/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10657258$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-01849230$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Nahoum, V</creatorcontrib><creatorcontrib>Roux, G</creatorcontrib><creatorcontrib>Anton, V</creatorcontrib><creatorcontrib>Rougé, P</creatorcontrib><creatorcontrib>Puigserver, A</creatorcontrib><creatorcontrib>Bischoff, H</creatorcontrib><creatorcontrib>Henrissat, B</creatorcontrib><creatorcontrib>Payan, F</creatorcontrib><title>Crystal structures of human pancreatic alpha-amylase in complex with carbohydrate and proteinaceous inhibitors</title><title>Biochemical journal</title><addtitle>Biochem J</addtitle><description>Crystal structures of human pancreatic alpha-amylase (HPA) in complex with naturally occurring inhibitors have been solved. The tetrasaccharide acarbose and a pseudo-pentasaccharide of the trestatin family produced identical continuous electron densities corresponding to a pentasaccharide species, spanning the -3 to +2 subsites of the enzyme, presumably resulting from transglycosylation. Binding of the acarviosine core linked to a glucose residue at subsites -1 to +2 appears to be a critical part of the interaction process between alpha-amylases and trestatin-derived inhibitors. Two crystal forms, obtained at different values of pH, for the complex of HPA with the protein inhibitor from Phaseolus vulgaris (alpha-amylase inhibitor) have been solved. The flexible loop typical of the mammalian alpha-amylases was shown to exist in two different conformations, suggesting that loop closure is pH-sensitive. Structural information is provided for the important inhibitor residue, Arg-74, which has not been observed previously in structural analyses.</description><subject>Acarbose - chemistry</subject><subject>Acarbose - metabolism</subject><subject>Acarbose - pharmacology</subject><subject>alpha-Amylases - antagonists & inhibitors</subject><subject>alpha-Amylases - chemistry</subject><subject>alpha-Amylases - metabolism</subject><subject>Amino Sugars - metabolism</subject><subject>Amino Sugars - pharmacology</subject><subject>Arginine - chemistry</subject><subject>Arginine - metabolism</subject><subject>Binding Sites</subject><subject>Biochemistry, Molecular Biology</subject><subject>Crystallography, X-Ray</subject><subject>Electrons</subject><subject>Enzyme Inhibitors - chemistry</subject><subject>Enzyme Inhibitors - metabolism</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Glycosylation</subject><subject>Humans</subject><subject>Hydrogen Bonding</subject><subject>Hydrogen-Ion Concentration</subject><subject>Lectins - chemistry</subject><subject>Lectins - metabolism</subject><subject>Lectins - pharmacology</subject><subject>Life Sciences</subject><subject>Models, Molecular</subject><subject>Molecular Sequence Data</subject><subject>Pancreas - enzymology</subject><subject>Plant Lectins</subject><subject>Plant Proteins - chemistry</subject><subject>Plant Proteins - metabolism</subject><subject>Plant Proteins - pharmacology</subject><subject>Polysaccharides - chemistry</subject><subject>Polysaccharides - metabolism</subject><subject>Polysaccharides - pharmacology</subject><subject>Protein Conformation</subject><subject>Structural Biology</subject><subject>Trisaccharides - chemistry</subject><subject>Trisaccharides - metabolism</subject><subject>Trisaccharides - pharmacology</subject><issn>0264-6021</issn><issn>1470-8728</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkU-L1EAQxRtR3HH1A3iRPgkeotV_Mul4EJZBXWHAi56bSqdiWpJ07O6szrc3YYZl9VJFdf3ea4rH2EsBbwVo-Q7kXhd7kOK90msD8YjthK6gMJU0j9nufn_FnqX0E0Bo0PCUXQnYl5UszY5Nh3hKGQeeclxcXiIlHjreLyNOfMbJRcLsHcdh7rHA8TRgIu4n7sI4D_SH__a55w5jE_pTGzETx6nlcwyZ_ISOwpJWvPeNzyGm5-xJh0OiF5d-zb5_-vjtcFscv37-crg5Fk7LOheyc40ohVG11iRrJUkpU6m6bIyu1ip02a6zaRWV0KwEtk3pqKxVR7pRoK7Zh7PvvDQjtY6mHHGwc_QjxpMN6O2_m8n39ke4s0JKMFqsBm_OBv1_stubo93eQBhdSwV3G_v68lkMvxZK2Y4-ORoGnLbzbQXGSNibFRRn0MWQUqTu3lmA3RK1W2J2S8xeEl01rx5e8kBxjlD9BVVrnb0</recordid><startdate>20000215</startdate><enddate>20000215</enddate><creator>Nahoum, V</creator><creator>Roux, G</creator><creator>Anton, V</creator><creator>Rougé, P</creator><creator>Puigserver, A</creator><creator>Bischoff, H</creator><creator>Henrissat, B</creator><creator>Payan, F</creator><general>Portland Press</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>7X8</scope><scope>1XC</scope><scope>5PM</scope></search><sort><creationdate>20000215</creationdate><title>Crystal structures of human pancreatic alpha-amylase in complex with carbohydrate and proteinaceous inhibitors</title><author>Nahoum, V ; Roux, G ; Anton, V ; Rougé, P ; Puigserver, A ; Bischoff, H ; Henrissat, B ; Payan, F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c429t-2fcb15183944e2932e3387395b84795b145d8738d3e50be29adb5ce593fe4b303</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Acarbose - chemistry</topic><topic>Acarbose - metabolism</topic><topic>Acarbose - pharmacology</topic><topic>alpha-Amylases - antagonists & inhibitors</topic><topic>alpha-Amylases - chemistry</topic><topic>alpha-Amylases - metabolism</topic><topic>Amino Sugars - metabolism</topic><topic>Amino Sugars - pharmacology</topic><topic>Arginine - chemistry</topic><topic>Arginine - metabolism</topic><topic>Binding Sites</topic><topic>Biochemistry, Molecular Biology</topic><topic>Crystallography, X-Ray</topic><topic>Electrons</topic><topic>Enzyme Inhibitors - chemistry</topic><topic>Enzyme Inhibitors - metabolism</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Glycosylation</topic><topic>Humans</topic><topic>Hydrogen Bonding</topic><topic>Hydrogen-Ion Concentration</topic><topic>Lectins - chemistry</topic><topic>Lectins - metabolism</topic><topic>Lectins - pharmacology</topic><topic>Life Sciences</topic><topic>Models, Molecular</topic><topic>Molecular Sequence Data</topic><topic>Pancreas - enzymology</topic><topic>Plant Lectins</topic><topic>Plant Proteins - chemistry</topic><topic>Plant Proteins - metabolism</topic><topic>Plant Proteins - pharmacology</topic><topic>Polysaccharides - chemistry</topic><topic>Polysaccharides - metabolism</topic><topic>Polysaccharides - pharmacology</topic><topic>Protein Conformation</topic><topic>Structural Biology</topic><topic>Trisaccharides - chemistry</topic><topic>Trisaccharides - metabolism</topic><topic>Trisaccharides - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nahoum, V</creatorcontrib><creatorcontrib>Roux, G</creatorcontrib><creatorcontrib>Anton, V</creatorcontrib><creatorcontrib>Rougé, P</creatorcontrib><creatorcontrib>Puigserver, A</creatorcontrib><creatorcontrib>Bischoff, H</creatorcontrib><creatorcontrib>Henrissat, B</creatorcontrib><creatorcontrib>Payan, F</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biochemical journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nahoum, V</au><au>Roux, G</au><au>Anton, V</au><au>Rougé, P</au><au>Puigserver, A</au><au>Bischoff, H</au><au>Henrissat, B</au><au>Payan, F</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Crystal structures of human pancreatic alpha-amylase in complex with carbohydrate and proteinaceous inhibitors</atitle><jtitle>Biochemical journal</jtitle><addtitle>Biochem J</addtitle><date>2000-02-15</date><risdate>2000</risdate><volume>346 Pt 1</volume><issue>1</issue><spage>201</spage><epage>208</epage><pages>201-208</pages><issn>0264-6021</issn><eissn>1470-8728</eissn><abstract>Crystal structures of human pancreatic alpha-amylase (HPA) in complex with naturally occurring inhibitors have been solved. The tetrasaccharide acarbose and a pseudo-pentasaccharide of the trestatin family produced identical continuous electron densities corresponding to a pentasaccharide species, spanning the -3 to +2 subsites of the enzyme, presumably resulting from transglycosylation. Binding of the acarviosine core linked to a glucose residue at subsites -1 to +2 appears to be a critical part of the interaction process between alpha-amylases and trestatin-derived inhibitors. Two crystal forms, obtained at different values of pH, for the complex of HPA with the protein inhibitor from Phaseolus vulgaris (alpha-amylase inhibitor) have been solved. The flexible loop typical of the mammalian alpha-amylases was shown to exist in two different conformations, suggesting that loop closure is pH-sensitive. Structural information is provided for the important inhibitor residue, Arg-74, which has not been observed previously in structural analyses.</abstract><cop>England</cop><pub>Portland Press</pub><pmid>10657258</pmid><doi>10.1042/0264-6021:3460201</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0264-6021 |
| ispartof | Biochemical journal, 2000-02, Vol.346 Pt 1 (1), p.201-208 |
| issn | 0264-6021 1470-8728 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1220841 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Acarbose - chemistry Acarbose - metabolism Acarbose - pharmacology alpha-Amylases - antagonists & inhibitors alpha-Amylases - chemistry alpha-Amylases - metabolism Amino Sugars - metabolism Amino Sugars - pharmacology Arginine - chemistry Arginine - metabolism Binding Sites Biochemistry, Molecular Biology Crystallography, X-Ray Electrons Enzyme Inhibitors - chemistry Enzyme Inhibitors - metabolism Enzyme Inhibitors - pharmacology Glycosylation Humans Hydrogen Bonding Hydrogen-Ion Concentration Lectins - chemistry Lectins - metabolism Lectins - pharmacology Life Sciences Models, Molecular Molecular Sequence Data Pancreas - enzymology Plant Lectins Plant Proteins - chemistry Plant Proteins - metabolism Plant Proteins - pharmacology Polysaccharides - chemistry Polysaccharides - metabolism Polysaccharides - pharmacology Protein Conformation Structural Biology Trisaccharides - chemistry Trisaccharides - metabolism Trisaccharides - pharmacology |
| title | Crystal structures of human pancreatic alpha-amylase in complex with carbohydrate and proteinaceous inhibitors |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-11T09%3A45%3A38IST&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=Crystal%20structures%20of%20human%20pancreatic%20alpha-amylase%20in%20complex%20with%20carbohydrate%20and%20proteinaceous%20inhibitors&rft.jtitle=Biochemical%20journal&rft.au=Nahoum,%20V&rft.date=2000-02-15&rft.volume=346%20Pt%201&rft.issue=1&rft.spage=201&rft.epage=208&rft.pages=201-208&rft.issn=0264-6021&rft.eissn=1470-8728&rft_id=info:doi/10.1042/0264-6021:3460201&rft_dat=%3Cproquest_pubme%3E70882068%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=70882068&rft_id=info:pmid/10657258&rfr_iscdi=true |