2gqv
|
High-resolution structure of a plasmid-encoded dihydrofolate reductase: pentagonal network of water molecules in the D2-symmetric active site
OverviewOverview
R67 plasmid-encoded dihydrofolate reductase (R67 DHFR) is an, NADPH-dependent homotetrameric enzyme that catalyzes the reduction of, dihydrofolate to tetrahydrofolate. The amino-acid sequence and molecular, architecture of R67 DHFR and its inhibitory properties toward folate, analogues are different from those of chromosomal DHFR. Here, the crystal, structure of R67 DHFR refined using 1.1 A resolution data is presented., Blocked full-matrix least-squares refinement without restraints resulted, in a final R factor of 11.4%. The anisotropic atomic displacement, parameters analyzed by Rosenfield matrices and translation-libration-screw, validation suggested four quasi-rigid domains. A total of ten Calpha-H...O, hydrogen bonds were identified between the beta-strands. There is, reasonable structural evidence that His62 is not protonated in the, tetramer, which is in accord with previous pH-profile studies. The side, chain of Gln67 that protrudes into the active site exhibits dual, conformation, a feature noticed for the first time owing to the, availability of atomic resolution data. The R67 DHFR active site is, unique: it has D2 symmetry and is a large active site with a pentagonal, network of water molecules and exposure of backbone atoms to solvent; the, central pore is favorable for planar ring-stacking interactions. The, geometrical shape, overall symmetry, local asymmetry and waters appear to, dominate the binding of ligands, catalysis and inhibition.
About this StructureAbout this Structure
2GQV is a Single protein structure of sequence from Escherichia coli. Active as Dihydrofolate reductase, with EC number 1.5.1.3 Full crystallographic information is available from OCA.
ReferenceReference
High-resolution structure of a plasmid-encoded dihydrofolate reductase: pentagonal network of water molecules in the D2-symmetric active site., Narayana N, Acta Crystallogr D Biol Crystallogr. 2006 Jul;62(Pt 7):695-706. Epub 2006, Jun 20. PMID:16790925
Page seeded by OCA on Wed Nov 21 11:21:09 2007