Steve Ealick's Research Group

Pyrococcus furiosus PurP

PDB files:

2R84, complexed with AICAR-AMP

2R85, complexed with AMP-AMP

2R86, complexed with Pi-ATP

2R87, complexed with Pi-ADP


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 (as seen in Methanocaldococcus jannaschii PurP) and IMP cyclohydrolase is encoded by the PurO gene. We determined the structure of a PurP ortholog from Pyrococcus furiosus, which is functionally unclassified, in three crystal forms.  With approximately 50% sequence identity, P. furiosus PurP is structurally homologous to M. jannaschii PurP.  A phylogenetic analysis was performed to explore the possible role of this functionally unclassified PurP.


Pyrococcus furiosus PurP belongs to the ATP-grasp superfamily and, as such it consists of three domains.

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The structure Pyrococcus furiosus PurP was determined in three crystal forms: two in the R32 space group and one in P2. PfPurP appeared to be predominantly trimeric in solution; however, PfPurP in all three crystal forms showed a common hexameric arrangement .

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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 with Arg202 built in alternate conformations. 

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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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