5UAO

Crystal structure of MibH, a lathipeptide tryptophan 5-halogenase

5UAO の概要

• エントリーDOI: 10.2210/pdb5uao/pdb
• 分子名称: Tryptophane-5-halogenase, FLAVIN-ADENINE DINUCLEOTIDE, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: halogenase, lanthipeptide, tryptophan, nai-107, oxidoreductase
• 由来する生物種: Microbispora sp. ATCC PTA-5024
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 238593.90

構造登録者

Cogan, D.P.,Nair, S.K. (登録日: 2016-12-19, 公開日: 2017-01-25, 最終更新日: 2024-10-16)

主引用文献

Ortega, M.A.,Cogan, D.P.,Mukherjee, S.,Garg, N.,Li, B.,Thibodeaux, G.N.,Maffioli, S.I.,Donadio, S.,Sosio, M.,Escano, J.,Smith, L.,Nair, S.K.,van der Donk, W.A.
Two Flavoenzymes Catalyze the Post-Translational Generation of 5-Chlorotryptophan and 2-Aminovinyl-Cysteine during NAI-107 Biosynthesis.
ACS Chem. Biol., 12:548-557, 2017

PubMed Abstract: Lantibiotics are ribosomally synthesized and post-translationally modified antimicrobial peptides containing thioether rings. In addition to these cross-links, the clinical candidate lantibiotic NAI-107 also possesses a C-terminal S-[(Z)-2-aminovinyl]-d-cysteine (AviCys) and a unique 5-chloro-l-tryptophan (ClTrp) moiety linked to its potent bioactivity. Bioinformatic and genetic analyses on the NAI-107 biosynthetic gene cluster identified mibH and mibD as genes encoding flavoenzymes responsible for the formation of ClTrp and AviCys, respectively. The biochemical basis for the installation of these modifications on NAI-107 and the substrate specificity of either enzyme is currently unknown. Using a combination of mass spectrometry, liquid chromatography, and bioinformatic analyses, we demonstrate that MibD is an FAD-dependent Cys decarboxylase and that MibH is an FADH-dependent Trp halogenase. Most FADH-dependent Trp halogenases halogenate free Trp, but MibH was only active when Trp was embedded within its cognate peptide substrate deschloro NAI-107. Structural comparison of the 1.88-Å resolution crystal structure of MibH with other flavin-dependent Trp halogenases revealed that subtle amino acid differences within the MibH substrate binding site generates a solvent exposed crevice presumably involved in determining the substrate specificity of this unusual peptide halogenase.

PubMed: 28032983
DOI: 10.1021/acschembio.6b01031

実験手法

X-RAY DIFFRACTION (1.88 Å)