Exploring the complex map of insulin polymorphism: a novel crystalline form in the presence of m‐cresol
In this study, the first crystal structure of a novel crystal form of human insulin bound to meta‐cresol in an acidic environment is reported. The combination of single‐crystal and powder X‐ray diffraction crystallography led to the detection of a previously unknown monoclinic phase (P21). The struc...
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Veröffentlicht in: | Acta crystallographica. Section D, Biological crystallography. Biological crystallography., 2020-04, Vol.76 (4), p.366-374 |
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container_title | Acta crystallographica. Section D, Biological crystallography. |
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creator | Karavassili, Fotini Valmas, Alexandros Dimarogona, Maria Giannopoulou, Anastasia E. Fili, Stavroula Norrman, Mathias Schluckebier, Gerd Beckers, Detlef Fitch, Andrew N. Margiolaki, I. |
description | In this study, the first crystal structure of a novel crystal form of human insulin bound to meta‐cresol in an acidic environment is reported. The combination of single‐crystal and powder X‐ray diffraction crystallography led to the detection of a previously unknown monoclinic phase (P21). The structure was identified from the powder patterns and was solved using single‐crystal diffraction data at 2.2 Å resolution. The unit‐cell parameters at pH 6.1 are a = 47.66, b = 70.36, c = 84.75 Å, β = 105.21°. The structure consists of two insulin hexamers per asymmetric unit. The potential use of this insulin form in microcrystalline drugs is discussed.
A novel monoclinic phase of human insulin co‐crystallized with m‐cresol was structurally characterized by means of powder and single‐crystal X‐ray diffraction. |
doi_str_mv | 10.1107/S2059798320002545 |
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A novel monoclinic phase of human insulin co‐crystallized with m‐cresol was structurally characterized by means of powder and single‐crystal X‐ray diffraction.</description><identifier>ISSN: 2059-7983</identifier><identifier>ISSN: 0907-4449</identifier><identifier>EISSN: 2059-7983</identifier><identifier>EISSN: 1399-0047</identifier><identifier>DOI: 10.1107/S2059798320002545</identifier><identifier>PMID: 32254061</identifier><language>eng</language><publisher>5 Abbey Square, Chester, Cheshire CH1 2HU, England: International Union of Crystallography</publisher><subject>Cresol ; Cresols - chemistry ; Crystal structure ; Crystallography ; Crystallography, X-Ray ; Crystals ; diabetes mellitus ; Diffraction ; Diffraction patterns ; Hexamers ; human insulin ; Humans ; Insulin ; Insulin - chemistry ; Models, Molecular ; m‐cresol ; Polymorphism ; powder diffraction ; Protein Multimerization ; Protein Structure, Quaternary ; single‐crystal diffraction ; synchrotron radiation ; X-Ray Diffraction</subject><ispartof>Acta crystallographica. Section D, Biological crystallography., 2020-04, Vol.76 (4), p.366-374</ispartof><rights>International Union of Crystallography, 2020</rights><rights>Copyright Wiley Subscription Services, Inc. Apr 2020</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3791-f36dc2b01c9666e7913957b94a671eb68e7bb10f5025597c65061d25194152373</citedby><cites>FETCH-LOGICAL-c3791-f36dc2b01c9666e7913957b94a671eb68e7bb10f5025597c65061d25194152373</cites><orcidid>0000-0003-4455-6054 ; 0000-0003-1696-0551 ; 0000-0003-4505-6131 ; 0000-0002-9768-5688</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1107%2FS2059798320002545$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1107%2FS2059798320002545$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32254061$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Karavassili, Fotini</creatorcontrib><creatorcontrib>Valmas, Alexandros</creatorcontrib><creatorcontrib>Dimarogona, Maria</creatorcontrib><creatorcontrib>Giannopoulou, Anastasia E.</creatorcontrib><creatorcontrib>Fili, Stavroula</creatorcontrib><creatorcontrib>Norrman, Mathias</creatorcontrib><creatorcontrib>Schluckebier, Gerd</creatorcontrib><creatorcontrib>Beckers, Detlef</creatorcontrib><creatorcontrib>Fitch, Andrew N.</creatorcontrib><creatorcontrib>Margiolaki, I.</creatorcontrib><title>Exploring the complex map of insulin polymorphism: a novel crystalline form in the presence of m‐cresol</title><title>Acta crystallographica. Section D, Biological crystallography.</title><addtitle>Acta Crystallogr D Struct Biol</addtitle><description>In this study, the first crystal structure of a novel crystal form of human insulin bound to meta‐cresol in an acidic environment is reported. The combination of single‐crystal and powder X‐ray diffraction crystallography led to the detection of a previously unknown monoclinic phase (P21). The structure was identified from the powder patterns and was solved using single‐crystal diffraction data at 2.2 Å resolution. The unit‐cell parameters at pH 6.1 are a = 47.66, b = 70.36, c = 84.75 Å, β = 105.21°. The structure consists of two insulin hexamers per asymmetric unit. The potential use of this insulin form in microcrystalline drugs is discussed.
A novel monoclinic phase of human insulin co‐crystallized with m‐cresol was structurally characterized by means of powder and single‐crystal X‐ray diffraction.</description><subject>Cresol</subject><subject>Cresols - chemistry</subject><subject>Crystal structure</subject><subject>Crystallography</subject><subject>Crystallography, X-Ray</subject><subject>Crystals</subject><subject>diabetes mellitus</subject><subject>Diffraction</subject><subject>Diffraction patterns</subject><subject>Hexamers</subject><subject>human insulin</subject><subject>Humans</subject><subject>Insulin</subject><subject>Insulin - chemistry</subject><subject>Models, Molecular</subject><subject>m‐cresol</subject><subject>Polymorphism</subject><subject>powder diffraction</subject><subject>Protein Multimerization</subject><subject>Protein Structure, Quaternary</subject><subject>single‐crystal diffraction</subject><subject>synchrotron radiation</subject><subject>X-Ray Diffraction</subject><issn>2059-7983</issn><issn>0907-4449</issn><issn>2059-7983</issn><issn>1399-0047</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc8uBTEYxRshCB7ARprY2Fz6Z9pO7cT_hFhgYTWZ6f2GkXY62ju4O4_gGT2JjosIC6u2J79z8p1-CK1Tsk0pUTuXjAitdM4ZIYSJTMyh5UEaDdr8j_sSWovxPkFUckV5toiWOEsGIukyag6fO-tD097iyR1g411n4Rm7ssO-xk0be9u0uPN26nzo7prodnGJW_8IFpswjZPSJgBw7YNL-EdIFyBCa2BIcG8vrya9vV1FC3VpI6x9nivo-ujwav9kdHZxfLq_dzYyXGk6qrkcG1YRarSUEpLEtVCVzkqpKFQyB1VVlNQidU79jRSpx5gJqjMqGFd8BW3NcrvgH3qIk8I10YC1ZQu-jwXjuWJCi5wldPMXeu_70KbpBkrmGZdUJIrOKBN8jAHqoguNK8O0oKQYVlH8WUXybHwm95WD8bfj6-MToGfAU2Nh-n9isXdzwI7PBUkbfAcJJ5L7</recordid><startdate>202004</startdate><enddate>202004</enddate><creator>Karavassili, Fotini</creator><creator>Valmas, Alexandros</creator><creator>Dimarogona, Maria</creator><creator>Giannopoulou, Anastasia E.</creator><creator>Fili, Stavroula</creator><creator>Norrman, Mathias</creator><creator>Schluckebier, Gerd</creator><creator>Beckers, Detlef</creator><creator>Fitch, Andrew N.</creator><creator>Margiolaki, I.</creator><general>International Union of Crystallography</general><general>Wiley Subscription Services, Inc</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>7QP</scope><scope>7SP</scope><scope>7SR</scope><scope>7TK</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>H8D</scope><scope>JG9</scope><scope>L7M</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-4455-6054</orcidid><orcidid>https://orcid.org/0000-0003-1696-0551</orcidid><orcidid>https://orcid.org/0000-0003-4505-6131</orcidid><orcidid>https://orcid.org/0000-0002-9768-5688</orcidid></search><sort><creationdate>202004</creationdate><title>Exploring the complex map of insulin polymorphism: a novel crystalline form in the presence of m‐cresol</title><author>Karavassili, Fotini ; Valmas, Alexandros ; Dimarogona, Maria ; Giannopoulou, Anastasia E. ; Fili, Stavroula ; Norrman, Mathias ; Schluckebier, Gerd ; Beckers, Detlef ; Fitch, Andrew N. ; Margiolaki, I.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3791-f36dc2b01c9666e7913957b94a671eb68e7bb10f5025597c65061d25194152373</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Cresol</topic><topic>Cresols - chemistry</topic><topic>Crystal structure</topic><topic>Crystallography</topic><topic>Crystallography, X-Ray</topic><topic>Crystals</topic><topic>diabetes mellitus</topic><topic>Diffraction</topic><topic>Diffraction patterns</topic><topic>Hexamers</topic><topic>human insulin</topic><topic>Humans</topic><topic>Insulin</topic><topic>Insulin - chemistry</topic><topic>Models, Molecular</topic><topic>m‐cresol</topic><topic>Polymorphism</topic><topic>powder diffraction</topic><topic>Protein Multimerization</topic><topic>Protein Structure, Quaternary</topic><topic>single‐crystal diffraction</topic><topic>synchrotron radiation</topic><topic>X-Ray Diffraction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Karavassili, Fotini</creatorcontrib><creatorcontrib>Valmas, Alexandros</creatorcontrib><creatorcontrib>Dimarogona, Maria</creatorcontrib><creatorcontrib>Giannopoulou, Anastasia E.</creatorcontrib><creatorcontrib>Fili, Stavroula</creatorcontrib><creatorcontrib>Norrman, Mathias</creatorcontrib><creatorcontrib>Schluckebier, Gerd</creatorcontrib><creatorcontrib>Beckers, Detlef</creatorcontrib><creatorcontrib>Fitch, Andrew N.</creatorcontrib><creatorcontrib>Margiolaki, I.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Aerospace Database</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>MEDLINE - Academic</collection><jtitle>Acta crystallographica. 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A novel monoclinic phase of human insulin co‐crystallized with m‐cresol was structurally characterized by means of powder and single‐crystal X‐ray diffraction.</abstract><cop>5 Abbey Square, Chester, Cheshire CH1 2HU, England</cop><pub>International Union of Crystallography</pub><pmid>32254061</pmid><doi>10.1107/S2059798320002545</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-4455-6054</orcidid><orcidid>https://orcid.org/0000-0003-1696-0551</orcidid><orcidid>https://orcid.org/0000-0003-4505-6131</orcidid><orcidid>https://orcid.org/0000-0002-9768-5688</orcidid></addata></record> |
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subjects | Cresol Cresols - chemistry Crystal structure Crystallography Crystallography, X-Ray Crystals diabetes mellitus Diffraction Diffraction patterns Hexamers human insulin Humans Insulin Insulin - chemistry Models, Molecular m‐cresol Polymorphism powder diffraction Protein Multimerization Protein Structure, Quaternary single‐crystal diffraction synchrotron radiation X-Ray Diffraction |
title | Exploring the complex map of insulin polymorphism: a novel crystalline form in the presence of m‐cresol |
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