Steve Ealick's Research Group


Thermatoga maritima S-Adenosylmethionine Decarboxylase


PDB files:

*1TLU, wild type T. maritima AdoMetDC

*1TMI, S63A mutant of T. maritima AdoMetDC

#3IWB T. maritima AdoMetDC in processed form

#3IWC T. maritima AdoMetDC with S-adenosylmethionine methyl ester

#3IWD T. maritima AdoMetDC complex with 5′-deoxy-5′-dimethylthioadenosine

Description:

Solution of the structure of Thermatoga maritima S-adenosylmethionine decarboxylase (TmAdoMetDC) continues our work on enzymes of the polyamine biosynthetic pathway. AdoMetDC is a critical regulatory enzyme in the polyamine synthetic pathway and is a target of drug design.The TmAdoMetDC structure provides striking evidence of an ancient gene duplication event resulting in the class 2 AdoMetDC enzymes (which incudes human and potato AdoMetDC's).

The architecture of each protomer (designated A and B) is a two-layer αβ-sandwich with an anti-parallel β-sheet flanked by two α-helices and a short 310-helix.

 

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The active form of TmAdoMetDC is an (αβ)2 dimer. Each protomer contains one active site that occurs at the dimer interface and also requires residues from the adjacent protomer.This dimer has a striking similarity to the monomer from potato AdoMetDC.

 

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A hydrogen bonding network connects the two active sites in the dimer interface of the TmAdoMetDC.

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References:

*Toms AV, Kinsland C, McCloskey DE, Pegg AE and Ealick SE. Evolutionary Links as Revealed by the Structure of Thermotoga maritima S-adenosylmethionine Decarboxylase. J. Biol. Chem. 279:33837-33846 (2004).

#Bale S, Baba K, McCloskey DE, and Ealick SE. Complexes of Thermotoga maritima S-Adenosylmethionine Decarboxylase Provide Insights into Substrate Specificity.Acta Crystallogr. D 66:181-189 (2010).



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