Structural determinants of reductive terpene cyclization in iridoid biosynthesis

TY - JOUR

T1 - Structural determinants of reductive terpene cyclization in iridoid biosynthesis

AU - Kries, Hajo

AU - Caputi, Lorenzo

AU - Stevenson, Clare E M

AU - Kamileen, Mohammed O

AU - Sherden, Nathaniel H

AU - Geu-Flores, Fernando

AU - Lawson, David M

AU - O'Connor, Sarah E

PY - 2016/1

Y1 - 2016/1

N2 - The carbon skeleton of ecologically and pharmacologically important iridoid monoterpenes is formed in a reductive cyclization reaction unrelated to canonical terpene cyclization. Here we report the crystal structure of the recently discovered iridoid cyclase (from Catharanthus roseus) bound to a mechanism-inspired inhibitor that illuminates substrate binding and catalytic function of the enzyme. Key features that distinguish iridoid synthase from its close homolog progesterone 5β-reductase are highlighted.

AB - The carbon skeleton of ecologically and pharmacologically important iridoid monoterpenes is formed in a reductive cyclization reaction unrelated to canonical terpene cyclization. Here we report the crystal structure of the recently discovered iridoid cyclase (from Catharanthus roseus) bound to a mechanism-inspired inhibitor that illuminates substrate binding and catalytic function of the enzyme. Key features that distinguish iridoid synthase from its close homolog progesterone 5β-reductase are highlighted.

KW - Catharanthus

KW - Crystallography, X-Ray

KW - Cyclization

KW - Iridoids

KW - Models, Molecular

KW - Oxidoreductases

KW - Plant Proteins

KW - Protein Conformation

KW - Terpenes

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/nchembio.1955

DO - 10.1038/nchembio.1955

M3 - Journal article

C2 - 26551396

SN - 1552-4450

VL - 12

SP - 6

EP - 8

JO - Nature Chemical Biology

JF - Nature Chemical Biology

IS - 1

ER -