1vdr
From Proteopedia
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DIHYDROFOLATE REDUCTASE
Overview
BACKGROUND: The proteins of halophilic archaea require high salt, concentrations both for stability and for activity, whereas they denature, at low ionic strength. The structural basis for this phenomenon is not yet, well understood. The crystal structure of dihydrofolate reductase (DHFR), from Haloferax volcanii (hv-DHFR) reported here provides the third example, of a structure of a protein from a halophilic organism. The enzyme is, considered moderately halophilic, as it retains activity and secondary, structure at monovalent salt concentrations as low as 0.5 M. RESULTS: The, crystal structure of hv-DHFR has been determined at 2.6 A resolution and, reveals the same overall fold as that of other DHFRs. The structure is in, the apo state, with an open conformation of the active-site gully, different from the open conformation seen in other DHFR structures. The, unique feature of hv-DHFR is a shift of the alpha helix encompassing, residues 46-51 and an accompanied altered conformation of the ensuing loop, relative to other DHFRs. Analysis of the charge distribution, amino acid, composition, packing and hydrogen-bonding pattern in hv-DHFR and its, non-halophilic homologs has been performed. CONCLUSIONS: The moderately, halophilic behavior of hv-DHFR is consistent with the lack of striking, structural features expected to occur in extremely halophilic proteins., The most notable feature of halophilicity is the presence of clusters of, non-interacting negatively charged residues. Such clusters are associated, with unfavorable electrostatic energy at low salt concentrations, and may, account for the instability of hv-DHFR at salt concentrations lower than, 0.5 M. With respect to catalysis, the open conformation seen here is, indicative of a conformational transition not reported previously. The, impact of this conformation on function and/or halophilicity is unknown.
About this Structure
1VDR is a Single protein structure of sequence from Haloferax volcanii with PO4 as ligand. Active as Dihydrofolate reductase, with EC number 1.5.1.3 Full crystallographic information is available from OCA.
Reference
Structural features of halophilicity derived from the crystal structure of dihydrofolate reductase from the Dead Sea halophilic archaeon, Haloferax volcanii., Pieper U, Kapadia G, Mevarech M, Herzberg O, Structure. 1998 Jan 15;6(1):75-88. PMID:9493269
Page seeded by OCA on Wed Nov 21 04:45:36 2007
