Steve Ealick's Research Group

Methanocaldococcus jannaschii PurP

PDB files:

2R7K, complexed with AICAR-AMPPCP

2R7L, complexed with AICAR-ATP

2R7M,complexed with FAICAR-ADP

2R7N,complexed with AMP-AMP


Purine biosynthesis requires ten enzymatic steps in higher organisms while prokaryotes require an additional enzyme for step six.  In most organisms steps nine and ten are catalyzed by the PurH gene product, a bifunctional enzyme with both 5-formaminoimidazole-4-carboxamide-5'-monophosphate ribonucleotide (FAICAR) synthase and inosine monophosphate (IMP) cyclohydrolase activity.  Recently it was discovered that Archaea utilize different enzymes to catalyze steps nine and ten.  An ATP dependent FAICAR synthetase is encoded by the PurP gene and IMP cyclohydrolase is encoded by the PurO gene. Methanocaldococcus jannaschii PurP enzyme for step nine belongs to the ATP grasp superfamily and is predicted to use a formylphosphate intermediate formed by an ATP-dependent phosphorylation. A homologue from Pyrococcus furiosus, PfPurP, has yet to be functionally classified.

Methanocaldococcus jannaschii PurP belongs to the ATP-grasp superfamily and is organized into A, B, and C domains.


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In crystals M. jannaschii PurP, as determined in the R32 space group, is a homohexamer with considerable interaction between the protomers.

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The active site cleft is formed by the assembly of the three domains. At right is a schematic of the AICAR binding site from the AICAR-ATP structure. 

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Zhang Y, White RH and Ealick SE. Crystal Structure and Function of 5-Formaminoimidazole-4-Carboxamide Ribonucleotide Synthetase from Methanocaldococcus jannaschii. Biochemistry 47:205-217 (2008).

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