6AL6

Crystal structure HpiC1 in P42 space group

6AL6 の概要

• エントリーDOI: 10.2210/pdb6al6/pdb
• 関連するPDBエントリー: 5WPP 5WPR 5WPS 5WPU
• 分子名称: 12-epi-hapalindole C/U synthase, CALCIUM ION (3 entities in total)
• 機能のキーワード: isomerase, cyclase
• 由来する生物種: Fischerella sp. ATCC 43239
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 49290.70

構造登録者

Newmister, S.A.,Li, S.,Garcia-Borras, M.,Sanders, J.N.,Yang, S.,Lowell, A.N.,Yu, F.,Smith, J.L.,Williams, R.M.,Houk, K.N.,Sherman, D.H. (登録日: 2017-08-07, 公開日: 2018-03-07, 最終更新日: 2023-10-04)

主引用文献

Newmister, S.A.,Li, S.,Garcia-Borras, M.,Sanders, J.N.,Yang, S.,Lowell, A.N.,Yu, F.,Smith, J.L.,Williams, R.M.,Houk, K.N.,Sherman, D.H.
Structural basis of the Cope rearrangement and cyclization in hapalindole biogenesis.
Nat. Chem. Biol., 14:345-351, 2018

PubMed Abstract: Hapalindole alkaloids are a structurally diverse class of cyanobacterial natural products defined by their varied polycyclic ring systems and diverse biological activities. These complex metabolites are generated from a common biosynthetic intermediate by the Stig cyclases in three mechanistic steps: a rare Cope rearrangement, 6-exo-trig cyclization, and electrophilic aromatic substitution. Here we report the structure of HpiC1, a Stig cyclase that catalyzes the formation of 12-epi-hapalindole U in vitro. The 1.5-Å structure revealed a dimeric assembly with two calcium ions per monomer and with the active sites located at the distal ends of the protein dimer. Mutational analysis and computational methods uncovered key residues for an acid-catalyzed [3,3]-sigmatropic rearrangement, as well as specific determinants that control the position of terminal electrophilic aromatic substitution, leading to a switch from hapalindole to fischerindole alkaloids.

PubMed: 29531360
DOI: 10.1038/s41589-018-0003-x

実験手法

X-RAY DIFFRACTION (2.088 Å)