7xvj
Crystal structure of CdpNPT in complex with harmol
Structural highlights
FunctionCDNTP_ASPFM Prenyltransferase that catalyzes reverse prenylation at position N-1 of tryptophan-containing cyclic dipeptides (PubMed:17525915, PubMed:35767141, PubMed:18383240, PubMed:19113967, PubMed:19421461, PubMed:33643664). Accepts only dimethylallyl diphosphate (DMAPP) as the prenyl donor but shows broad substrate specificities toward its aromatic substrates (PubMed:17525915, PubMed:18383240, PubMed:19113967, PubMed:19421461, PubMed:33643664, PubMed:35767141). Shows also tryptophan aminopeptidase activity with preference for linear peptides containing a tryptophanyl moiety at the N-terminus (PubMed:18635009).[1] [2] [3] [4] [5] [6] [7] Publication Abstract from PubMedCdpNPT from Aspergillus fumigatus is a fungal indole prenyltransferase (IPT) with remarkable substrate promiscuity to generate prenylated compounds. Our first investigation of the catalytic potential of CdpNPT against a beta-carboline, harmol (1), revealed that the enzyme also accepts 1 as the prenyl acceptor with dimethylallyl diphosphate (DMAPP) as the prenyl donor and selectively prenylates the C-6 position of 1 by the "regular-type" dimethylallylation to produce 6-(3-dimethylallyl)harmol (2). Furthermore, our X-ray crystal structure analysis of the C-His(6)-tagged CdpNPT (38-440) truncated mutant complexed with 1 and docking studies of DMAPP to the crystal structure of the CdpNPT (38-440) mutant suggested that CdpNPT could employ the two-step prenylation system to produce 2. Enzymatic formation of a prenyl beta-carboline by a fungal indole prenyltransferase.,Hamdy SA, Kodama T, Nakashima Y, Han X, Matsui T, Morita H J Nat Med. 2022 Sep;76(4):873-879. doi: 10.1007/s11418-022-01635-0. Epub 2022 Jun , 29. PMID:35767141[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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