Characterization of the aminocarboxycyclopropane-forming enzyme CmaC.

Characterization of the aminocarboxycyclopropane-forming enzyme CmaC. Research Abstract Details 

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Characterization of the aminocarboxycyclopropane-forming enzyme CmaC. Abstract Text:

Wendy L Kelly,Michael T Boyne,Ellen Yeh,David A Vosburg,Danica P Galoni?,Neil L Kelleher,Christopher T Walsh,

The biosynthesis of the coronamic acid fragment of the pseudomonal phytotoxin coronatine involves construction of the cyclopropane ring from a gamma-chloro-L-allo-Ile intermediate while covalently tethered as a phosphopantetheinyl thioester to the carrier protein CmaD. The cyclopropane-forming catalyst is CmaC, catalyzing an intramolecular displacement of the gamma-Cl group by the alpha carbon. CmaC can be isolated as a Zn2+ protein with about 10-fold higher activity over the apo form. CmaC will not cyclize free gamma-chloro amino acids or their S-N-acetylcysteamine (NAC) thioester derivatives but will recognize some other carrier protein scaffolds. Turnover numbers of 5 min-1 are observed for Zn-CmaC, acting on gamma-chloro-L-aminobutyryl-S-CmaD, generating 1-aminocyclopropane-1-carbonyl (ACC)-S-CmaD. Products were detected either while still tethered to the phosphopantetheinyl prosthetic arm by mass spectrometry or after thioesterase-mediated release and derivatization of the free amino acid. In D2O, CmaC catalyzed exchange of one deuterium into the aminobutyryl moiety of the gamma-Cl-aminoacyl-S-CmaD, whereas the product ACC-S-CmaD lacked the deuterium, consistent with a competition for a gamma-Cl-aminobutyryl alpha-carbanion between reprotonation and cyclization. CmaC-mediated cyclization yielded solely ACC, resulting from C-C bond formation and no azetidine carboxylate from an alternate N-C cyclization. CmaC could cyclize gamma,gamma-dichloroaminobutyryl to the Cl-ACC product but did not cyclize delta- or epsilon-chloroaminoacyl-S-CmaD substrates.

Characterization of the aminocarboxycyclopropane-forming enzyme CmaC. Publishing Authors By Initials

WL Kelly,MT Boyne,E Yeh,DA Vosburg,DP Galoni?,NL Kelleher,CT Walsh,

For similar enzymes and coenzymes: enzymes: hydrolases: esterases: thiolester hydrolases research abstracts see: enzymes and coenzymes: enzymes: hydrolases: esterases: thiolester hydrolases research

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Characterization of the aminocarboxycyclopropane-forming enzyme CmaC. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Biochemistry

VOLUME: 46

Page Numbers: 359-68

Journal Abbreviation: Biochemistry

ISSN: 0006-2960

DAY: 16

MONTH: Jan

YEAR: 2007

Characterization of the aminocarboxycyclopropane-forming enzyme CmaC. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 370623

Characterization of the aminocarboxycyclopropane-forming enzyme CmaC. Keywords Mesh Terms:

KEYWORDS: Thiolester Hydrolases

MESH TERMS: metabolism

Chemical & Substance for Abstract: Characterization of the aminocarboxycyclopropane-forming enzyme CmaC. Information

Substance Name: Thiolester Hydrolases

Registry Number: EC 3.1.2.-

Grant and Affiliation Information for Characterization of the aminocarboxycyclopropane-forming enzyme CmaC.

AFFILIATION: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM 20011

ACRONYM: GM

MEDLINETA: Biochemistry

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