5DOZ

Crystal structure of JamJ enoyl reductase (NADPH bound)

Summary for 5DOZ

• Entry DOI: 10.2210/pdb5doz/pdb
• Related: 5DOV 5DP1 5DP2
• Descriptor: JamJ, ACETATE ION, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (4 entities in total)
• Functional Keywords: enoyl reductase, polyketide synthase, nadph, cyclopropane, oxidoreductase
• Biological source: Lyngbya majuscula
• Total number of polymer chains: 3
• Total formula weight: 116035.64

Authors

Khare, D.,Smith, J.L. (deposition date: 2015-09-11, release date: 2015-11-18, Last modification date: 2023-09-27)

Primary citation

Khare, D.,Hale, W.A.,Tripathi, A.,Gu, L.,Sherman, D.H.,Gerwick, W.H.,Hakansson, K.,Smith, J.L.
Structural Basis for Cyclopropanation by a Unique Enoyl-Acyl Carrier Protein Reductase.
Structure, 23:2213-2223, 2015

PubMed Abstract: The natural product curacin A, a potent anticancer agent, contains a rare cyclopropane group. The five enzymes for cyclopropane biosynthesis are highly similar to enzymes that generate a vinyl chloride moiety in the jamaicamide natural product. The structural biology of this remarkable catalytic adaptability is probed with high-resolution crystal structures of the curacin cyclopropanase (CurF ER), an in vitro enoyl reductase (JamJ ER), and a canonical curacin enoyl reductase (CurK ER). The JamJ and CurK ERs catalyze NADPH-dependent double bond reductions typical of enoyl reductases (ERs) of the medium-chain dehydrogenase reductase (MDR) superfamily. Cyclopropane formation by CurF ER is specified by a short loop which, when transplanted to JamJ ER, confers cyclopropanase activity on the chimeric enzyme. Detection of an adduct of NADPH with the model substrate crotonyl-CoA provides indirect support for a recent proposal of a C2-ene intermediate on the reaction pathway of MDR enoyl-thioester reductases.

PubMed: 26526850
DOI: 10.1016/j.str.2015.09.013

Experimental method

X-RAY DIFFRACTION (2.26 Å)