Steve Ealick's Research Group
Methanobacterium thermoautotrophicum PurO
2NTM, unliganded PurO
Inosine 5′-monophosphate (IMP) cyclohydrolase catalyzes the cyclization of 5-formaminoimidazole-4-carboxamide ribonucleotide (FAICAR) to IMP in the final step of de novo purine biosynthesis. In Archaea PurO performs this function while PurH is the enzyme in Bacteria.
The Methanobacterium thermoautotrophicum PurO (MthPurO) monomer adopts an NTN hydrolase fold showing a four-layered α-β-β-α core structure with two antiparallel β-sheets packed against each other covered by α-helices.
|MthPurO exists as a box-shaped tetramer, both in solution and in the crystal form P32 that we analyzed.The monomers are arranged so that each makes contacts with the other three monomers.|
The IMP molecule is bound at the deep pocket between
the two central central b-sheets. All amino
acid residues in the pocket are absolutely conserved within
all PurO sequences. Dashed lines indicate the hydrogen bonds.
Kang, Y.-N., Tran, A., White, R. H., and Ealick, S. E. A Novel Function for the NTN Hydrolase Fold Demonstrated by the Structure of an Archeal Inosine Monophosphate Cyclohydrolase, Biochemistry 46:5050-5062 (2007).