PDBsum entry 1vdr

Oxidoreductase

PDB id: 1vdr

Contents

Protein chains

157 a.a. *

Ligands

PO4 ×3

Waters ×80

* Residue conservation analysis

PDB id:

1vdr

Name:

Oxidoreductase

Title:

Dihydrofolate reductase

Structure:

Dihydrofolate reductase. Chain: a, b. Synonym: dhfr. Ec: 1.5.1.3

Source:

Haloferax volcanii. Organism_taxid: 2246. Other_details: formerly halobacterium volcanii

Biol. unit:

Dimer (from PQS)

Resolution:

2.55Å R-factor: 0.184 R-free: 0.300

Authors:

U.Pieper,O.Herzberg

Key ref:

U.Pieper et al. (1998). Structural features of halophilicity derived from the crystal structure of dihydrofolate reductase from the Dead Sea halophilic archaeon, Haloferax volcanii. Structure, 6, 75-88. PubMed id: 9493269 DOI: 10.1016/S0969-2126(98)00009-4

Date:

30-Nov-97 Release date: 25-Feb-98

Protein chains

P15093  (DYRA_HALVD) -  Dihydrofolate reductase HdrA from Haloferax volcanii (strain ATCC 29605 / DSM 3757 / JCM 8879 / NBRC 14742 / NCIMB 2012 / VKM B-1768 / DS2)

Seq: 162 a.a.

Struc: 157 a.a.

Enzyme reactions

• Enzyme class: E.C.1.5.1.3 - dihydrofolate reductase.
• Pathway: Folate Coenzymes
• Reaction: (6S)-5,6,7,8-tetrahydrofolate + NADP⁺ = 7,8-dihydrofolate + NADPH + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/S0969-2126(98)00009-4

Structure 6:75-88 (1998)

PubMed id: 9493269

Structural features of halophilicity derived from the crystal structure of dihydrofolate reductase from the Dead Sea halophilic archaeon, Haloferax volcanii.

U.Pieper, G.Kapadia, M.Mevarech, O.Herzberg.

ABSTRACT

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.

Selected figure(s)

Figure 3.
Figure 3. Superposition of the Cα trace of hv-DHFR (solid line), ec-DHFR in the closed conformation (long dashes; PDB entry code 1rx9) and ec-DHFR in the occluded conformation (short dashes; PDB entry code 1rx5). Every tenth residue of hv-DHFR is labeled.

Figure 6.
Figure 6. Stereo representation of two clusters of negatively charged residues in hv-DHFR. Water molecules are depicted as black spheres and hydrogen bonds as dashed lines. (a) Intramolecular cluster; (b) intermolecular cluster at the interface of three molecules.

The above figures are reprinted by permission from Cell Press: Structure (1998, 6, 75-88) copyright 1998.

Figures were selected by an automated process.