3H5A

Crystal structure of E. coli MccB

3H5A の概要

• エントリーDOI: 10.2210/pdb3h5a/pdb
• 関連するPDBエントリー: 3H5N 3H5R 3H9G 3H9J 3H9Q
• 分子名称: MccB protein, ZINC ION (2 entities in total)
• 機能のキーワード: ubiquitin-activating enzymes, microcin, protein structure, mccc7, peptide antibiotics, n-p bond formation, transferase
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 161056.18

構造登録者

Regni, C.A.,Roush, R.F.,Miller, D.,Nourse, A.,Walsh, C.T.,Schulman, B.A. (登録日: 2009-04-21, 公開日: 2009-06-16, 最終更新日: 2024-02-21)

主引用文献

Regni, C.A.,Roush, R.F.,Miller, D.J.,Nourse, A.,Walsh, C.T.,Schulman, B.A.
How the MccB bacterial ancestor of ubiquitin E1 initiates biosynthesis of the microcin C7 antibiotic.
Embo J., 28:1953-1964, 2009

PubMed Abstract: The 39-kDa Escherichia coli enzyme MccB catalyses a remarkable posttranslational modification of the MccA heptapeptide during the biosynthesis of microcin C7 (MccC7), a 'Trojan horse' antibiotic. The approximately 260-residue C-terminal region of MccB is homologous to ubiquitin-like protein (UBL) activating enzyme (E1) adenylation domains. Accordingly, MccB-catalysed C-terminal MccA-acyl-adenylation is reminiscent of the E1-catalysed activation reaction. However, unlike E1 substrates, which are UBLs with a C-terminal di-glycine sequence, MccB's substrate, MccA, is a short peptide with an essential C-terminal Asn. Furthermore, after an intramolecular rearrangement of MccA-acyl-adenylate, MccB catalyses a second, unique reaction, producing a stable phosphoramidate-linked analogue of acyl-adenylated aspartic acid. We report six-crystal structures of MccB in apo, substrate-, intermediate-, and inhibitor-bound forms. Structural and kinetic analyses reveal a novel-peptide clamping mechanism for MccB binding to heptapeptide substrates and a dynamic-active site for catalysing dual adenosine triphosphate-consuming reactions. The results provide insight into how a distinctive member of the E1 superfamily carries out two-step activation for generating the peptidyl-antibiotic MccC7.

PubMed: 19494832
DOI: 10.1038/emboj.2009.146

実験手法

X-RAY DIFFRACTION (2.8 Å)