Ensemble refinement of the protein crystal structure of a glyoxylate/hydroxypyruvate reductase from Homo sapiens
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[GRHPR_HUMAN] Defects in GRHPR are the cause of hyperoxaluria primary type 2 (HP2) [MIM:260000]; also known as primary hyperoxaluria type II (PH2). HP2 is a disorder where the main clinical manifestation is calcium oxalate nephrolithiasis though chronic as well as terminal renal insufficiency has been described. It is characterized by an elevated urinary excretion of oxalate and L-glycerate.
[GRHPR_HUMAN] Enzyme with hydroxy-pyruvate reductase, glyoxylate reductase and D-glycerate dehydrogenase enzymatic activities. Reduces hydroxypyruvate to D-glycerate, glyoxylate to glycolate oxidizes D-glycerate to hydroxypyruvate.
Publication Abstract from PubMed
X-ray crystallography typically uses a single set of coordinates and B factors to describe macromolecular conformations. Refinement of multiple copies of the entire structure has been previously used in specific cases as an alternative means of representing structural flexibility. Here, we systematically validate this method by using simulated diffraction data, and we find that ensemble refinement produces better representations of the distributions of atomic positions in the simulated structures than single-conformer refinements. Comparison of principal components calculated from the refined ensembles and simulations shows that concerted motions are captured locally, but that correlations dissipate over long distances. Ensemble refinement is also used on 50 experimental structures of varying resolution and leads to decreases in R(free) values, implying that improvements in the representation of flexibility observed for the simulated structures may apply to real structures. These gains are essentially independent of resolution or data-to-parameter ratio, suggesting that even structures at moderate resolution can benefit from ensemble refinement.
Ensemble refinement of protein crystal structures: validation and application.,Levin EJ, Kondrashov DA, Wesenberg GE, Phillips GN Jr Structure. 2007 Sep;15(9):1040-52. PMID:17850744
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.