3NNM

Halogenase domain from CurA module (crystal form IV)

Summary for 3NNM

• Entry DOI: 10.2210/pdb3nnm/pdb
• Related: 3NNF 3NNJ 3NNL
• Descriptor: CurA, FORMIC ACID (3 entities in total)
• Functional Keywords: non-haem fe(ii)/alpha-ketoglutarate-dependent enzyme, catalyzes a cryptic chlorination, biosynthetic protein
• Biological source: Lyngbya majuscula
• Total number of polymer chains: 2
• Total formula weight: 80420.55

Authors

Khare, D.,Smith, J.L. (deposition date: 2010-06-23, release date: 2010-07-28, Last modification date: 2024-04-03)

Primary citation

Khare, D.,Wang, B.,Gu, L.,Razelun, J.,Sherman, D.H.,Gerwick, W.H.,Hakansson, K.,Smith, J.L.
Conformational switch triggered by alpha-ketoglutarate in a halogenase of curacin A biosynthesis
Proc.Natl.Acad.Sci.USA, 107:14099-14104, 2010

PubMed Abstract: 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 Fe(2+), O(2) and alpha-ketoglutarate (alphaKG) 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 alphaKG binding. The open form represents ligand-free enzyme, preventing substrate from entering the active site until both alphaKG and chloride are bound, while the closed form represents the holoenzyme with alphaKG 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 alphaKG leading to chlorination of an early pathway intermediate.

PubMed: 20660778
DOI: 10.1073/pnas.1006738107

Experimental method

X-RAY DIFFRACTION (2.69 Å)