PDBsum entry 1dgp

Lyase

PDB id: 1dgp

Contents

Protein chains

290 a.a. *

Ligands

FOF ×2

FOH ×2

Waters ×200

* Residue conservation analysis

PDB id:

1dgp

Name:

Lyase

Title:

Aristolochene synthase farnesol complex

Structure:

Aristolochene synthase. Chain: a, b. Synonym: sesquiterpene cyclase, as. Engineered: yes

Source:

Penicillium roqueforti. Organism_taxid: 5082. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

2.80Å R-factor: 0.234 R-free: 0.264

Authors:

J.M.Caruthers,I.Kang,D.E.Cane,D.W.Christianson

Key ref:

J.M.Caruthers et al. (2000). Crystal structure determination of aristolochene synthase from the blue cheese mold, Penicillium roqueforti. J Biol Chem, 275, 25533-25539. PubMed id: 10825154 DOI: 10.1074/jbc.M000433200

Date:

24-Nov-99 Release date: 07-Feb-01

Protein chains

Q03471  (PRX2_PENRO) -  Aristolochene synthase from Penicillium roqueforti

Seq: 342 a.a.

Struc: 290 a.a.

Enzyme reactions

• Enzyme class: E.C.4.2.3.9 - aristolochene synthase.
• Pathway: Germacrene derived sesquiterpenoid biosynthesis
• Reaction: (2E,6E)-farnesyl diphosphate = ⁺-aristolochene + diphosphate

(2E,6E)-farnesyl diphosphate = (+)-aristolochene (Bound ligand (Het Group name = FOF) matches with 82.35% similarity) + diphosphate

• Cofactor: Mg(2+); Mn(2+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1074/jbc.M000433200

J Biol Chem 275:25533-25539 (2000)

PubMed id: 10825154

Crystal structure determination of aristolochene synthase from the blue cheese mold, Penicillium roqueforti.

J.M.Caruthers, I.Kang, M.J.Rynkiewicz, D.E.Cane, D.W.Christianson.

ABSTRACT

The 2.5-A resolution crystal structure of recombinant aristolochene synthase from the blue cheese mold, Penicillium roqueforti, is the first of a fungal terpenoid cyclase. The structure of the enzyme reveals active site features that participate in the cyclization of the universal sesquiterpene cyclase substrate, farnesyl diphosphate, to form the bicyclic hydrocarbon aristolochene. Metal-triggered carbocation formation initiates the cyclization cascade, which proceeds through multiple complex intermediates to yield one exclusive structural and stereochemical isomer of aristolochene. Structural homology of this fungal cyclase with plant and bacterial terpenoid cyclases, despite minimal amino acid sequence identity, suggests divergence from a common, primordial ancestor in the evolution of terpene biosynthesis.

Selected figure(s)

Figure 4.
Fig. 4. Evolution of sesquiterpene biosynthetic pathways. Structural comparison of terpenoid synthases reveals that each enzyme in the biosynthetic pathway is a variation of the "terpenoid synthase fold," despite insignificant amino acid sequence identities. This structural comparison indicates evolutionary divergence of animal, plant, bacterial, and fungal cyclases from a common primordial ancestor.

Figure 6.
Fig. 6. Structure-based mechanism of P. roqueforti aristolochene synthase. Models of the enzyme complexed with substrate, intermediates, and product are shown; salient mechanistic details are outlined in the text and appear schematically in Fig. 5. Briefly, farnesyl diphosphate binds in the unique productive conformation prior to the departure of the diphosphate leaving group (A). The initial cyclization yields the germacrene A intermediate through formation of the C-1-C-10 bond (B) (the diphosphate leaving group is not shown for clarity). Protonation of C-6 by Tyr-92 accompanied by C-2-C-7 bond formation closes the 10-membered ring of germacrene A to form the bicyclic eudesmane cation intermediate (C). A 1,2-hydride transfer, accompanied by a C-14 methyl migration and the elimination of H 8, yield aristolochene (D). Figure prepared with AVS (44).

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2000, 275, 25533-25539) copyright 2000.

Figures were selected by an automated process.