Figure 1: D2HGDH mutations in DLBCL. | Nature Communications

Figure 1: D2HGDH mutations in DLBCL.

From: D2HGDH regulates alpha-ketoglutarate levels and dioxygenase function by modulating IDH2

Figure 1

(a) Sequencing traces representative of each of the five unique mutations found in DLBCL; arrows indicate the nucleotide change, and amino acid substitution is listed at the bottom. Constitutive DNA was available from two patients with D2HGDH mutant tumours (R212W variant), and one case is shown here. The G131fs21X, A208T and R421H mutations were found in cell lines, whereas A426T was found both in primary tumours and cell lines (Supplementary Table 1). (b) All four missense variants identified in DLBCL map to fully conserved residues. (c) Display of the closest structural homologue of human D2HGDH (dehydrogenase from Rhodopseudomonas palustris, PDB 3PM9) identified in the RCSB protein data bank. Orthogonal views of the structure are shown, with the non-covalently bound FAD displayed, as well as sidechains of the residues targeted by missense mutations in DLBCL (shaded yellow) or in D-2-hydroxyglutaric aciduria (shaded red). In both diseases, the mutations clustered to two structural areas—a region of possible contact with the FAD and/or the enzyme’s substrate (see expansion subpanel), or an uncharacterized outside loop containing the residues V399, R419, R421, A426 and A446. The structures shown were generated using the programme UCSF Chimera32.

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