5WGV
Crystal Structure of MalA' C112S/C128S, premalbrancheamide complex
Summary for 5WGV
| Entry DOI | 10.2210/pdb5wgv/pdb |
| Descriptor | Flavin-dependent halogenase, FLAVIN-ADENINE DINUCLEOTIDE, CADMIUM ION, ... (8 entities in total) |
| Functional Keywords | flavin-dependent halogenase, malbrancheamide, zinc, zn, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor |
| Biological source | Malbranchea aurantiaca |
| Total number of polymer chains | 1 |
| Total formula weight | 77040.20 |
| Authors | Fraley, A.E.,Smith, J.L. (deposition date: 2017-07-14, release date: 2017-08-16, Last modification date: 2023-10-04) |
| Primary citation | Fraley, A.E.,Garcia-Borras, M.,Tripathi, A.,Khare, D.,Mercado-Marin, E.V.,Tran, H.,Dan, Q.,Webb, G.P.,Watts, K.R.,Crews, P.,Sarpong, R.,Williams, R.M.,Smith, J.L.,Houk, K.N.,Sherman, D.H. Function and Structure of MalA/MalA', Iterative Halogenases for Late-Stage C-H Functionalization of Indole Alkaloids. J. Am. Chem. Soc., 139:12060-12068, 2017 Cited by PubMed Abstract: Malbrancheamide is a dichlorinated fungal indole alkaloid isolated from both Malbranchea aurantiaca and Malbranchea graminicola that belongs to a family of natural products containing a characteristic bicyclo[2.2.2]diazaoctane core. The introduction of chlorine atoms on the indole ring of malbrancheamide differentiates it from other members of this family and contributes significantly to its biological activity. In this study, we characterized the two flavin-dependent halogenases involved in the late-stage halogenation of malbrancheamide in two different fungal strains. MalA and MalA' catalyze the iterative dichlorination and monobromination of the free substrate premalbrancheamide as the final steps in the malbrancheamide biosynthetic pathway. Two unnatural bromo-chloro-malbrancheamide analogues were generated through MalA-mediated chemoenzymatic synthesis. Structural analysis and computational studies of MalA' in complex with three substrates revealed that the enzyme represents a new class of zinc-binding flavin-dependent halogenases and provides new insights into a potentially unique reaction mechanism. PubMed: 28777910DOI: 10.1021/jacs.7b06773 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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