Novel recombinant insulin analogue with flexible C-terminus in B chain. NMR structure of biosynthetic engineered A22G-B31K-B32R human insulin monomer in water/acetonitrile solution
A tertiary structure of recombinant A22G-B31K-B32R-human insulin monomer (insulin GKR) has been characterized by 1H, 13C NMR at natural isotopic abundance using NOESY, TOCSY, 1H/13C-GHSQC, and 1H/13C-GHSQC-TOCSY spectra. Translational diffusion studies indicate the monomer structure in water/acetoni...
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| Veröffentlicht in: | International journal of biological macromolecules 2011-11, Vol.49 (4), p.548-554 |
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| creator | Borowicz, Piotr Bocian, Wojciech Sitkowski, Jerzy Bednarek, Elżbieta Mikiewicz-Syguła, Diana Błażej-Sosnowska, Sylwia Bogiel, Monika Rusek, Dorota Kurzynoga, Dariusz Kozerski, Lech |
| description | A tertiary structure of recombinant A22G-B31K-B32R-human insulin monomer (insulin GKR) has been characterized by 1H, 13C NMR at natural isotopic abundance using NOESY, TOCSY, 1H/13C-GHSQC, and 1H/13C-GHSQC-TOCSY spectra. Translational diffusion studies indicate the monomer structure in water/acetonitrile (65/35vol.%). CSI analysis confirms existence of secondary structure motifs present in human insulin standard (HIS). Both techniques allow to establish that in this solvent recombinant insulin GKR exists as a monomer. Starting from structures calculated by the program CYANA, two different refinement protocols used molecular dynamics simulated annealing with the program AMBER; in vacuum (AMBER_VC), and including a generalized Born solvent model (AMBER_GB). From these calculations an ensemble of 20 structures of lowest energy was chosen which represents the tertiary structure of studied insulin. Here we present novel insulin with added A22G amino acid which interacts with β-turn environment resulting in high flexibility of B chain C-terminus. |
| doi_str_mv | 10.1016/j.ijbiomac.2011.06.008 |
| format | Article |
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NMR structure of biosynthetic engineered A22G-B31K-B32R human insulin monomer in water/acetonitrile solution</title><source>MEDLINE</source><source>ScienceDirect Journals (5 years ago - present)</source><creator>Borowicz, Piotr ; Bocian, Wojciech ; Sitkowski, Jerzy ; Bednarek, Elżbieta ; Mikiewicz-Syguła, Diana ; Błażej-Sosnowska, Sylwia ; Bogiel, Monika ; Rusek, Dorota ; Kurzynoga, Dariusz ; Kozerski, Lech</creator><creatorcontrib>Borowicz, Piotr ; Bocian, Wojciech ; Sitkowski, Jerzy ; Bednarek, Elżbieta ; Mikiewicz-Syguła, Diana ; Błażej-Sosnowska, Sylwia ; Bogiel, Monika ; Rusek, Dorota ; Kurzynoga, Dariusz ; Kozerski, Lech</creatorcontrib><description>A tertiary structure of recombinant A22G-B31K-B32R-human insulin monomer (insulin GKR) has been characterized by 1H, 13C NMR at natural isotopic abundance using NOESY, TOCSY, 1H/13C-GHSQC, and 1H/13C-GHSQC-TOCSY spectra. Translational diffusion studies indicate the monomer structure in water/acetonitrile (65/35vol.%). CSI analysis confirms existence of secondary structure motifs present in human insulin standard (HIS). Both techniques allow to establish that in this solvent recombinant insulin GKR exists as a monomer. Starting from structures calculated by the program CYANA, two different refinement protocols used molecular dynamics simulated annealing with the program AMBER; in vacuum (AMBER_VC), and including a generalized Born solvent model (AMBER_GB). From these calculations an ensemble of 20 structures of lowest energy was chosen which represents the tertiary structure of studied insulin. Here we present novel insulin with added A22G amino acid which interacts with β-turn environment resulting in high flexibility of B chain C-terminus.</description><identifier>ISSN: 0141-8130</identifier><identifier>EISSN: 1879-0003</identifier><identifier>DOI: 10.1016/j.ijbiomac.2011.06.008</identifier><identifier>PMID: 21704065</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>13C ; Acetonitriles - chemistry ; Amino Acid Motifs ; Amino Acid Substitution ; Diffusion ; H2O/CD3CN solvent ; Humans ; Insulin, Regular, Human - analogs & derivatives ; Insulin, Regular, Human - chemistry ; Magnetic Resonance Spectroscopy ; NMR ; Protein Engineering ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; recombinant A22G-B31K-B32R-human insulin ; Reference Standards ; Solutions ; Tertiary structure of monomer ; Water - chemistry</subject><ispartof>International journal of biological macromolecules, 2011-11, Vol.49 (4), p.548-554</ispartof><rights>2011 Elsevier B.V.</rights><rights>Copyright © 2011 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c297t-cb43cae2605bd80764ef893f5a69e66e25a4240fb408485532708b3c914ae63e3</citedby><cites>FETCH-LOGICAL-c297t-cb43cae2605bd80764ef893f5a69e66e25a4240fb408485532708b3c914ae63e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ijbiomac.2011.06.008$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21704065$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Borowicz, Piotr</creatorcontrib><creatorcontrib>Bocian, Wojciech</creatorcontrib><creatorcontrib>Sitkowski, Jerzy</creatorcontrib><creatorcontrib>Bednarek, Elżbieta</creatorcontrib><creatorcontrib>Mikiewicz-Syguła, Diana</creatorcontrib><creatorcontrib>Błażej-Sosnowska, Sylwia</creatorcontrib><creatorcontrib>Bogiel, Monika</creatorcontrib><creatorcontrib>Rusek, Dorota</creatorcontrib><creatorcontrib>Kurzynoga, Dariusz</creatorcontrib><creatorcontrib>Kozerski, Lech</creatorcontrib><title>Novel recombinant insulin analogue with flexible C-terminus in B chain. NMR structure of biosynthetic engineered A22G-B31K-B32R human insulin monomer in water/acetonitrile solution</title><title>International journal of biological macromolecules</title><addtitle>Int J Biol Macromol</addtitle><description>A tertiary structure of recombinant A22G-B31K-B32R-human insulin monomer (insulin GKR) has been characterized by 1H, 13C NMR at natural isotopic abundance using NOESY, TOCSY, 1H/13C-GHSQC, and 1H/13C-GHSQC-TOCSY spectra. Translational diffusion studies indicate the monomer structure in water/acetonitrile (65/35vol.%). CSI analysis confirms existence of secondary structure motifs present in human insulin standard (HIS). Both techniques allow to establish that in this solvent recombinant insulin GKR exists as a monomer. Starting from structures calculated by the program CYANA, two different refinement protocols used molecular dynamics simulated annealing with the program AMBER; in vacuum (AMBER_VC), and including a generalized Born solvent model (AMBER_GB). From these calculations an ensemble of 20 structures of lowest energy was chosen which represents the tertiary structure of studied insulin. Here we present novel insulin with added A22G amino acid which interacts with β-turn environment resulting in high flexibility of B chain C-terminus.</description><subject>13C</subject><subject>Acetonitriles - chemistry</subject><subject>Amino Acid Motifs</subject><subject>Amino Acid Substitution</subject><subject>Diffusion</subject><subject>H2O/CD3CN solvent</subject><subject>Humans</subject><subject>Insulin, Regular, Human - analogs & derivatives</subject><subject>Insulin, Regular, Human - chemistry</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>NMR</subject><subject>Protein Engineering</subject><subject>Protein Structure, Quaternary</subject><subject>Protein Structure, Tertiary</subject><subject>recombinant A22G-B31K-B32R-human insulin</subject><subject>Reference Standards</subject><subject>Solutions</subject><subject>Tertiary structure of monomer</subject><subject>Water - chemistry</subject><issn>0141-8130</issn><issn>1879-0003</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc9u1DAQhy0EokvhFSrfOCW1ncRxbrSrUhClSBWcLcc76c4qsYv_tPS9eEC82rZXLh7Z-mZ-Hn2EnHBWc8bl6a7G3Yh-MbYWjPOayZox9YqsuOqHijHWvCYrxlteKd6wI_Iuxl15lR1Xb8mR4D1ry2VF_l77e5hpAOuXEZ1xiaKLeUZHjTOzv81AHzBt6TTDHxxnoOsqQVjQ5VhIek7t1qCr6fX3GxpTyDblANRPtPwuPrq0hYSWgrtFBxBgQ8-EuKzOG_6tHOKGbvNi3Evm4p1fIOwnP5iSc2osJO8wBSzR0c85oXfvyZvJzBE-PNVj8uvzxc_1l-rqx-XX9dlVZcXQp8qObWMNCMm6caNYL1uY1NBMnZEDSAmiM61o2TS2TLWq6xrRMzU2duCtAdlAc0w-HubeBf87Q0x6wWhhno0Dn6NWqu-7QfGhkPJA2uBjDDDpu4CLCY-aM70Xpnf6WZjeC9NM6iKsNJ48ReRxgc1L27OhAnw6AFAWvUcIOloEZ2GDRVrSG4__y_gHa0Ssow</recordid><startdate>20111101</startdate><enddate>20111101</enddate><creator>Borowicz, Piotr</creator><creator>Bocian, Wojciech</creator><creator>Sitkowski, Jerzy</creator><creator>Bednarek, Elżbieta</creator><creator>Mikiewicz-Syguła, Diana</creator><creator>Błażej-Sosnowska, Sylwia</creator><creator>Bogiel, Monika</creator><creator>Rusek, Dorota</creator><creator>Kurzynoga, Dariusz</creator><creator>Kozerski, Lech</creator><general>Elsevier B.V</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></search><sort><creationdate>20111101</creationdate><title>Novel recombinant insulin analogue with flexible C-terminus in B chain. NMR structure of biosynthetic engineered A22G-B31K-B32R human insulin monomer in water/acetonitrile solution</title><author>Borowicz, Piotr ; Bocian, Wojciech ; Sitkowski, Jerzy ; Bednarek, Elżbieta ; Mikiewicz-Syguła, Diana ; Błażej-Sosnowska, Sylwia ; Bogiel, Monika ; Rusek, Dorota ; Kurzynoga, Dariusz ; Kozerski, Lech</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c297t-cb43cae2605bd80764ef893f5a69e66e25a4240fb408485532708b3c914ae63e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>13C</topic><topic>Acetonitriles - chemistry</topic><topic>Amino Acid Motifs</topic><topic>Amino Acid Substitution</topic><topic>Diffusion</topic><topic>H2O/CD3CN solvent</topic><topic>Humans</topic><topic>Insulin, Regular, Human - analogs & derivatives</topic><topic>Insulin, Regular, Human - chemistry</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>NMR</topic><topic>Protein Engineering</topic><topic>Protein Structure, Quaternary</topic><topic>Protein Structure, Tertiary</topic><topic>recombinant A22G-B31K-B32R-human insulin</topic><topic>Reference Standards</topic><topic>Solutions</topic><topic>Tertiary structure of monomer</topic><topic>Water - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Borowicz, Piotr</creatorcontrib><creatorcontrib>Bocian, Wojciech</creatorcontrib><creatorcontrib>Sitkowski, Jerzy</creatorcontrib><creatorcontrib>Bednarek, Elżbieta</creatorcontrib><creatorcontrib>Mikiewicz-Syguła, Diana</creatorcontrib><creatorcontrib>Błażej-Sosnowska, Sylwia</creatorcontrib><creatorcontrib>Bogiel, Monika</creatorcontrib><creatorcontrib>Rusek, Dorota</creatorcontrib><creatorcontrib>Kurzynoga, Dariusz</creatorcontrib><creatorcontrib>Kozerski, Lech</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><jtitle>International journal of biological macromolecules</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Borowicz, Piotr</au><au>Bocian, Wojciech</au><au>Sitkowski, Jerzy</au><au>Bednarek, Elżbieta</au><au>Mikiewicz-Syguła, Diana</au><au>Błażej-Sosnowska, Sylwia</au><au>Bogiel, Monika</au><au>Rusek, Dorota</au><au>Kurzynoga, Dariusz</au><au>Kozerski, Lech</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Novel recombinant insulin analogue with flexible C-terminus in B chain. NMR structure of biosynthetic engineered A22G-B31K-B32R human insulin monomer in water/acetonitrile solution</atitle><jtitle>International journal of biological macromolecules</jtitle><addtitle>Int J Biol Macromol</addtitle><date>2011-11-01</date><risdate>2011</risdate><volume>49</volume><issue>4</issue><spage>548</spage><epage>554</epage><pages>548-554</pages><issn>0141-8130</issn><eissn>1879-0003</eissn><abstract>A tertiary structure of recombinant A22G-B31K-B32R-human insulin monomer (insulin GKR) has been characterized by 1H, 13C NMR at natural isotopic abundance using NOESY, TOCSY, 1H/13C-GHSQC, and 1H/13C-GHSQC-TOCSY spectra. Translational diffusion studies indicate the monomer structure in water/acetonitrile (65/35vol.%). CSI analysis confirms existence of secondary structure motifs present in human insulin standard (HIS). Both techniques allow to establish that in this solvent recombinant insulin GKR exists as a monomer. Starting from structures calculated by the program CYANA, two different refinement protocols used molecular dynamics simulated annealing with the program AMBER; in vacuum (AMBER_VC), and including a generalized Born solvent model (AMBER_GB). From these calculations an ensemble of 20 structures of lowest energy was chosen which represents the tertiary structure of studied insulin. Here we present novel insulin with added A22G amino acid which interacts with β-turn environment resulting in high flexibility of B chain C-terminus.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>21704065</pmid><doi>10.1016/j.ijbiomac.2011.06.008</doi><tpages>7</tpages></addata></record> |
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| ispartof | International journal of biological macromolecules, 2011-11, Vol.49 (4), p.548-554 |
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| subjects | 13C Acetonitriles - chemistry Amino Acid Motifs Amino Acid Substitution Diffusion H2O/CD3CN solvent Humans Insulin, Regular, Human - analogs & derivatives Insulin, Regular, Human - chemistry Magnetic Resonance Spectroscopy NMR Protein Engineering Protein Structure, Quaternary Protein Structure, Tertiary recombinant A22G-B31K-B32R-human insulin Reference Standards Solutions Tertiary structure of monomer Water - chemistry |
| title | Novel recombinant insulin analogue with flexible C-terminus in B chain. NMR structure of biosynthetic engineered A22G-B31K-B32R human insulin monomer in water/acetonitrile solution |
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