3grs
REFINED STRUCTURE OF GLUTATHIONE REDUCTASE AT 1.54 ANGSTROMS RESOLUTION
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OverviewOverview
The crystal structure of human glutathione reductase has been established, at 1.54 A resolution using a restrained least-squares refinement method., Based on 77,690 independent reflections of better than 10 A resolution, a, final R-factor of 18.6% was obtained with a model obeying standard, geometry within 0.025 A in bond lengths and 2.4 degrees in bond angles., The final 2Fo-Fc electron density map allows for the distinction of, carbon, nitrogen and oxygen atoms with temperature factors below about 25, A2. Apart from 461 amino acid residues and the prosthetic group FAD, the, model contains 524 solvent molecules, about 118 of which can be considered, an integral part of the enzyme. The largest solvent cluster is at the, dimer interface and contains 104 interconnected solvent molecules, part of, which are organized in a warped sheet-like structure. The main-chain, dihedral angles are well-concentrated in the allowed regions of the, Ramachandran plot. The spread of dihedral angles in beta-pleated sheets is, much larger than in alpha-helices and especially in alpha-helix cores, indicating the higher plasticity of beta-structures. The analysis revealed, a large amount of 3(10)-helix. The side-chain conformations cluster at the, staggered positions, and show well-defined preferences. Also, a mobility, gradient is observed for side-chains. Non-polar and polar side-chains show, average temperature factor increases per bond of 10% and 25%, respectively. A number of alternative conformations of internal, side-chains, in particular serines and methionines, have been detected., The extended FAD molecule also shows a mobility gradient between the very, rigid flavin (mean value of B) = 8.7 A2) and the more mobile adenine (mean, value of B = 16.2 A2). The entire active center is particularly well, ordered, with temperature factors around 10 A2. The dimer interface, consists of a rigid contact area, which is well conserved in the, Escherichia coli enzyme, and a flexible area that is not. Altogether, the, buried surfaces at the crystal contacts are half as large as at the dimer, interface, but less specific. The refined structure shows clearly that, there are no buried cations compensating the charge of the pyrophosphate, moiety of FAD. The flavin deviates slightly from standard geometry, which, is possibly caused by the polypeptide environment. In contrast to an, earlier interpretation, atom N5 of the flavin can accommodate a proton, and it is conceivable that this proton proceeds to the redox-active, disulfide.(ABSTRACT TRUNCATED AT 400 WORDS)
DiseaseDisease
Known disease associated with this structure: Hemolytic anemia due to glutathione reductase deficiency OMIM:[138300]
About this StructureAbout this Structure
3GRS is a Single protein structure of sequence from Homo sapiens with PO4 and FAD as ligands. This structure superseeds the now removed PDB entries 2GRS and 1GRS. Active as Glutathione-disulfide reductase, with EC number 1.8.1.7 Full crystallographic information is available from OCA.
ReferenceReference
Refined structure of glutathione reductase at 1.54 A resolution., Karplus PA, Schulz GE, J Mol Biol. 1987 Jun 5;195(3):701-29. PMID:3656429
Page seeded by OCA on Mon Nov 12 23:48:23 2007