3IE5

Crystal structure of Hyp-1 protein from Hypericum perforatum (St John's wort) involved in hypericin biosynthesis

Summary for 3IE5

• Entry DOI: 10.2210/pdb3ie5/pdb
• Related: 1BV1 1ICX 1IFV 1XDF 2FLH 2QIM 3E85
• Descriptor: Phenolic oxidative coupling protein Hyp-1, CHLORIDE ION, TRIETHYLENE GLYCOL, ... (8 entities in total)
• Functional Keywords: hypericin, st john's wort, depression, allergy, pr-10 protein, cytokinin, plant hormones, polyethylene glycol, peg, pathogenesis-related protein, plant defense, plant protein, biosynthetic protein
• Biological source: Hypericum perforatum (St. John's wort)
• Total number of polymer chains: 2
• Total formula weight: 39100.09

Authors

Michalska, K.,Fernandes, H.,Sikorski, M.M.,Jaskolski, M. (deposition date: 2009-07-22, release date: 2009-11-10, Last modification date: 2024-10-30)

Primary citation

Michalska, K.,Fernandes, H.,Sikorski, M.M.,Jaskolski, M.
Crystal structure of Hyp-1, a St. John's wort protein implicated in the biosynthesis of hypericin
J.Struct.Biol., 169:161-171, 2010

PubMed Abstract: Hypericin, a red-colored naphtodianthrone, is a natural product synthesized in the medicinal plant Hypericum perforatum, widely known as St. John's wort. Hypericin has been attracting a growing attention of the pharmaceutical industry because of its potential application in various therapies, including the treatment of depression. In vivo, hypericin is synthesized by dimerization of emodin in a complicated multistep reaction that is reportedly catalyzed by a small (17.8kDa) protein, Hyp-1. Based on relatively low sequence similarity ( approximately 50%), Hyp-1 has been tentatively classified as a plant PR-10 (pathogenesis-related class 10) protein. Members of the PR-10 family are ubiquitous plant proteins associated with stress control and tissue differentiation but with no clearly understood molecular mechanism. They have, however, a well-defined folding canon, consisting of an extended antiparallel beta-sheet wrapped around a C-terminal alpha-helix, enclosing in the protein interior a huge cavity, in which various hydrophobic ligands can be bound. Apart from Hyp-1, only two other PR-10 members have been found to possess enzymatic activity (S-norcoclaurine synthase and TcmN aromatase/cyclase). In this paper, we report a high-resolution crystal structure of Hyp-1, confirming that it indeed has a PR-10 fold. The protein binds multiple polyethylene glycol molecules, some of which occupy the hydrophobic cavity. The crystallographic model illustrates a high degree of conformational adaptability of both interacting partners for efficient binding. We have been unable, however, to dimerize emodin to hypericin using Hyp-1 as biocatalyst. This puzzling result does not have a clear explanation at this time.

PubMed: 19853038
DOI: 10.1016/j.jsb.2009.10.008

Experimental method

X-RAY DIFFRACTION (1.688 Å)