Structural analysis of an open active site conformation of nonheme iron halogenase CytC3
CytC3, a member of the recently discovered class of nonheme Fe(II) and R-ketoglutarate (RKG)- dependent halogenases, catalyzes the double chlorination of L-2-aminobutyric acid (Aba) to produce a known Streptomyces antibiotic, gamma,gamma-dichloroaminobutyrate. Unlike the majority of the Fe(II)-RKG...
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| Format: | Article |
| Language: | en_US |
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American Chemical Society
2011
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| Online Access: | http://hdl.handle.net/1721.1/64708 https://orcid.org/0000-0001-5486-2755 |
| _version_ | 1811074685325017088 |
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| author | Wong, Cintyu Fujimori, Danica Galonic Walsh, Christopher T. Drennan, Catherine L. |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Wong, Cintyu Fujimori, Danica Galonic Walsh, Christopher T. Drennan, Catherine L. |
| author_sort | Wong, Cintyu |
| collection | MIT |
| description | CytC3, a member of the recently discovered class of nonheme Fe(II) and R-ketoglutarate (RKG)-
dependent halogenases, catalyzes the double chlorination of L-2-aminobutyric acid (Aba) to produce a
known Streptomyces antibiotic, gamma,gamma-dichloroaminobutyrate. Unlike the majority of the Fe(II)-RKG-dependentenzymes that catalyze hydroxylation reactions, halogenases catalyze a transfer of halides. To examinethe important enzymatic features that discriminate between chlorination and hydroxylation, the crystal structures of CytC3 both with and without RKG/Fe(II) have been solved to 2.2 Å resolution. These structures capture CytC3 in an open active site conformation, in which no chloride is bound to iron. Comparison of the open conformation of CytC3 with the closed conformation of another nonheme iron halogenase, SyrB2, suggests two important criteria for creating an enzyme-bound FesCl catalyst: (1) the presence of a hydrogen-bonding network between the chloride and surrounding residues, and (2) the presence of a hydrophobic pocket in which the chloride resides. |
| first_indexed | 2024-09-23T09:53:44Z |
| format | Article |
| id | mit-1721.1/64708 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:53:44Z |
| publishDate | 2011 |
| publisher | American Chemical Society |
| record_format | dspace |
| spelling | mit-1721.1/647082022-09-26T14:22:02Z Structural analysis of an open active site conformation of nonheme iron halogenase CytC3 Wong, Cintyu Fujimori, Danica Galonic Walsh, Christopher T. Drennan, Catherine L. Massachusetts Institute of Technology. Department of Chemistry Drennan, Catherine L. Drennan, Catherine L. Wong, Cintyu CytC3, a member of the recently discovered class of nonheme Fe(II) and R-ketoglutarate (RKG)- dependent halogenases, catalyzes the double chlorination of L-2-aminobutyric acid (Aba) to produce a known Streptomyces antibiotic, gamma,gamma-dichloroaminobutyrate. Unlike the majority of the Fe(II)-RKG-dependentenzymes that catalyze hydroxylation reactions, halogenases catalyze a transfer of halides. To examinethe important enzymatic features that discriminate between chlorination and hydroxylation, the crystal structures of CytC3 both with and without RKG/Fe(II) have been solved to 2.2 Å resolution. These structures capture CytC3 in an open active site conformation, in which no chloride is bound to iron. Comparison of the open conformation of CytC3 with the closed conformation of another nonheme iron halogenase, SyrB2, suggests two important criteria for creating an enzyme-bound FesCl catalyst: (1) the presence of a hydrogen-bonding network between the chloride and surrounding residues, and (2) the presence of a hydrophobic pocket in which the chloride resides. National Institutes of Health (U.S.) (grant GM65337) National Institutes of Health (U.S.) (grant GM49338) Massachusetts Institute of Technology. Center for Environmental Health Sciences Massachusetts Institute of Technology. Center for Environmental Health Sciences (NIEHS P30 ES002109) Damon Runyon Cancer Research Foundation Damon Runyon Cancer Research Foundation (Postdoctoral Fellowship DRG-1893-05) 2011-06-29T19:09:34Z 2011-06-29T19:09:34Z 2009-03 Article http://purl.org/eprint/type/JournalArticle 1520-5126 0002-7863 http://hdl.handle.net/1721.1/64708 Wong, Cintyu et al. “Structural Analysis of an Open Active Site Conformation of Nonheme Iron Halogenase CytC3.” Journal of the American Chemical Society 131.13 (2009) : 4872-4879. © 2009 American Chemical Society. https://orcid.org/0000-0001-5486-2755 en_US http:/dx.doi.org/10.1021/ja8097355 Journal of the American Chemical Society Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Chemical Society Prof. Drennan via Erja Kajosalo |
| spellingShingle | Wong, Cintyu Fujimori, Danica Galonic Walsh, Christopher T. Drennan, Catherine L. Structural analysis of an open active site conformation of nonheme iron halogenase CytC3 |
| title | Structural analysis of an open active site conformation of nonheme iron halogenase CytC3 |
| title_full | Structural analysis of an open active site conformation of nonheme iron halogenase CytC3 |
| title_fullStr | Structural analysis of an open active site conformation of nonheme iron halogenase CytC3 |
| title_full_unstemmed | Structural analysis of an open active site conformation of nonheme iron halogenase CytC3 |
| title_short | Structural analysis of an open active site conformation of nonheme iron halogenase CytC3 |
| title_sort | structural analysis of an open active site conformation of nonheme iron halogenase cytc3 |
| url | http://hdl.handle.net/1721.1/64708 https://orcid.org/0000-0001-5486-2755 |
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