Conformational switch triggered by [alpha]-ketoglutarate in a halogenase of curacin A biosynthesis
The CurA halogenase (Hal) catalyzes a cryptic chlorination leading to cyclopropane ring formation in the synthesis of the natural product curacin A. Hal belongs to a family of enzymes that use ..., ... and α-ketoglutarate (αKG) to perform a variety of halogenation reactions in natural product biosyn...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2010-08, Vol.107 (32), p.14099 |
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| container_issue | 32 |
| container_start_page | 14099 |
| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 107 |
| creator | Khare, Dheeraj Wang, Bo Gu, Liangcai Razelun, Jamie Sherman, David H Gerwick, William H Håkansson, Kristina Smith, Janet L |
| description | The CurA halogenase (Hal) catalyzes a cryptic chlorination leading to cyclopropane ring formation in the synthesis of the natural product curacin A. Hal belongs to a family of enzymes that use ..., ... and α-ketoglutarate (αKG) to perform a variety of halogenation reactions in natural product biosynthesis. Crystal structures of the enzyme in five ligand states reveal strikingly different open and closed conformations dependent on αKG binding. The open form represents ligand-free enzyme, preventing substrate from entering the active site until both αKG and chloride are bound, while the closed form represents the holoenzyme with αKG and chloride coordinated to iron. Candidate amino acid residues involved in substrate recognition were identified by site-directed mutagenesis. These new structures provide direct evidence of a conformational switch driven by αKG leading to chlorination of an early pathway intermediate. (ProQuest: ... denotes formulae/symbols omitted.) |
| doi_str_mv | 10.1073/pnas.1006738107 |
| format | Article |
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(ANL), Argonne, IL (United States). Advanced Photon Source (APS)</creatorcontrib><description>The CurA halogenase (Hal) catalyzes a cryptic chlorination leading to cyclopropane ring formation in the synthesis of the natural product curacin A. Hal belongs to a family of enzymes that use ..., ... and α-ketoglutarate (αKG) to perform a variety of halogenation reactions in natural product biosynthesis. Crystal structures of the enzyme in five ligand states reveal strikingly different open and closed conformations dependent on αKG binding. The open form represents ligand-free enzyme, preventing substrate from entering the active site until both αKG and chloride are bound, while the closed form represents the holoenzyme with αKG and chloride coordinated to iron. Candidate amino acid residues involved in substrate recognition were identified by site-directed mutagenesis. These new structures provide direct evidence of a conformational switch driven by αKG leading to chlorination of an early pathway intermediate. 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(ANL), Argonne, IL (United States). Advanced Photon Source (APS)</creatorcontrib><title>Conformational switch triggered by [alpha]-ketoglutarate in a halogenase of curacin A biosynthesis</title><title>Proceedings of the National Academy of Sciences - PNAS</title><description>The CurA halogenase (Hal) catalyzes a cryptic chlorination leading to cyclopropane ring formation in the synthesis of the natural product curacin A. Hal belongs to a family of enzymes that use ..., ... and α-ketoglutarate (αKG) to perform a variety of halogenation reactions in natural product biosynthesis. Crystal structures of the enzyme in five ligand states reveal strikingly different open and closed conformations dependent on αKG binding. The open form represents ligand-free enzyme, preventing substrate from entering the active site until both αKG and chloride are bound, while the closed form represents the holoenzyme with αKG and chloride coordinated to iron. Candidate amino acid residues involved in substrate recognition were identified by site-directed mutagenesis. These new structures provide direct evidence of a conformational switch driven by αKG leading to chlorination of an early pathway intermediate. (ProQuest: ... denotes formulae/symbols omitted.)</description><subject>AMINO ACIDS</subject><subject>BIOSYNTHESIS</subject><subject>Catalysis</subject><subject>Chemical synthesis</subject><subject>CHLORIDES</subject><subject>CHLORINATION</subject><subject>Chlorine</subject><subject>CRYSTAL STRUCTURE</subject><subject>ENZYMES</subject><subject>HALOGENATION</subject><subject>IRON</subject><subject>MATERIALS SCIENCE</subject><subject>MUTAGENESIS</subject><subject>RESIDUES</subject><subject>SUBSTRATES</subject><subject>SYNTHESIS</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><recordid>eNpFkM1LxDAQxYMoWFfPXoP36rRJm8lxWfyCBS97EylpmrZZa7MmKbL_vREFT2_48WaG9wi5LuC2AMHuDrMKaYJaMEzghGQFyCKvuYRTkgGUIkde8nNyEcIeAGSFkJF24-be-Q8VrZvVRMOXjXqk0dthMN50tD3SVzUdRvWWv5vohmmJyqtoqJ2poqOa3GDSZ0NdT_XilU58TVvrwnGOowk2XJKzXk3BXP3piuwe7nebp3z78vi8WW9zV3GWS82wZwoROyyF7A1r607rgnHAutdoWgFl1VVcInJZa66MTCHwZwMUdGxFbn7PuhBtE7SNRo_azbPRsUm9lJVg_6aDd5-LCbHZu8Wn4KERnJcFQsXYN2ImY3k</recordid><startdate>20100812</startdate><enddate>20100812</enddate><creator>Khare, Dheeraj</creator><creator>Wang, Bo</creator><creator>Gu, Liangcai</creator><creator>Razelun, Jamie</creator><creator>Sherman, David H</creator><creator>Gerwick, William H</creator><creator>Håkansson, Kristina</creator><creator>Smith, Janet L</creator><general>National Academy of Sciences</general><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>OTOTI</scope></search><sort><creationdate>20100812</creationdate><title>Conformational switch triggered by [alpha]-ketoglutarate in a halogenase of curacin A biosynthesis</title><author>Khare, Dheeraj ; Wang, Bo ; Gu, Liangcai ; Razelun, Jamie ; Sherman, David H ; Gerwick, William H ; Håkansson, Kristina ; Smith, Janet L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-o543-9c38f3a888d8279fe3b6dcc134086fc8eb7025d54988496c4ae90098a8880a0d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>AMINO ACIDS</topic><topic>BIOSYNTHESIS</topic><topic>Catalysis</topic><topic>Chemical synthesis</topic><topic>CHLORIDES</topic><topic>CHLORINATION</topic><topic>Chlorine</topic><topic>CRYSTAL STRUCTURE</topic><topic>ENZYMES</topic><topic>HALOGENATION</topic><topic>IRON</topic><topic>MATERIALS SCIENCE</topic><topic>MUTAGENESIS</topic><topic>RESIDUES</topic><topic>SUBSTRATES</topic><topic>SYNTHESIS</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Khare, Dheeraj</creatorcontrib><creatorcontrib>Wang, Bo</creatorcontrib><creatorcontrib>Gu, Liangcai</creatorcontrib><creatorcontrib>Razelun, Jamie</creatorcontrib><creatorcontrib>Sherman, David H</creatorcontrib><creatorcontrib>Gerwick, William H</creatorcontrib><creatorcontrib>Håkansson, Kristina</creatorcontrib><creatorcontrib>Smith, Janet L</creatorcontrib><creatorcontrib>Argonne National Lab. 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| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2010-08, Vol.107 (32), p.14099 |
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| source | Jstor Complete Legacy; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | AMINO ACIDS BIOSYNTHESIS Catalysis Chemical synthesis CHLORIDES CHLORINATION Chlorine CRYSTAL STRUCTURE ENZYMES HALOGENATION IRON MATERIALS SCIENCE MUTAGENESIS RESIDUES SUBSTRATES SYNTHESIS |
| title | Conformational switch triggered by [alpha]-ketoglutarate in a halogenase of curacin A biosynthesis |
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