3VC2

Crystal structure of geranyl diphosphate C-methyltransferase from Streptomyces coelicolor A3(2) in complex with Mg2+, geranyl diphosphate, and S-adenosyl-L-homocysteine

Summary for 3VC2

• Entry DOI: 10.2210/pdb3vc2/pdb
• Related: 3VC1
• Descriptor: Geranyl diphosphate 2-C-methyltransferase, MAGNESIUM ION, S-ADENOSYL-L-HOMOCYSTEINE, ... (6 entities in total)
• Functional Keywords: rossmann fold, methyltransferase fold, sam-dependent methyltransferase, c-methyltransferase, terpenoid biosynthesis, 2-methylisoborneol biosynthesis, transferase
• Biological source: Streptomyces coelicolor
• Total number of polymer chains: 12
• Total formula weight: 426544.13

Authors

Koksal, M.,Christianson, D.W. (deposition date: 2012-01-03, release date: 2012-04-11, Last modification date: 2023-09-13)

Primary citation

Koksal, M.,Chou, W.K.,Cane, D.E.,Christianson, D.W.
Structure of Geranyl Diphosphate C-Methyltransferase from Streptomyces coelicolor and Implications for the Mechanism of Isoprenoid Modification.
Biochemistry, 51:3003-3010, 2012

PubMed Abstract: Geranyl diphosphate C-methyltransferase (GPPMT) from Streptomyces coelicolor A3(2) is the first methyltransferase discovered that modifies an acyclic isoprenoid diphosphate, geranyl diphosphate (GPP), to yield a noncanonical acyclic allylic diphosphate product, 2-methylgeranyl diphosphate, which serves as the substrate for a subsequent cyclization reaction catalyzed by a terpenoid cyclase, methylisoborneol synthase. Here, we report the crystal structures of GPPMT in complex with GPP or the substrate analogue geranyl S-thiolodiphosphate (GSPP) along with S-adenosyl-L-homocysteine in the cofactor binding site, resulting from in situ demethylation of S-adenosyl-L-methionine, at 2.05 or 1.82 Å resolution, respectively. These structures suggest that both GPP and GSPP can undergo catalytic methylation in crystalline GPPMT, followed by dissociation of the isoprenoid product. S-Adenosyl-L-homocysteine remains bound in the active site, however, and does not exchange with a fresh molecule of cofactor S-adenosyl-L-methionine. These structures provide important clues about the molecular mechanism of the reaction, especially with regard to the face of the 2,3 double bond of GPP that is methylated as well as the stabilization of the resulting carbocation intermediate through cation-π interactions.

PubMed: 22455498
DOI: 10.1021/bi300109c

Experimental method

X-RAY DIFFRACTION (2.046 Å)