5NHG

Crystal structure of the human dihydrolipoamide dehydrogenase

Summary for 5NHG

• Entry DOI: 10.2210/pdb5nhg/pdb
• Descriptor: Dihydrolipoyl dehydrogenase, mitochondrial, FLAVIN-ADENINE DINUCLEOTIDE, 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, ... (5 entities in total)
• Functional Keywords: dihydrolipoamide dehydrogenase, e3 subunit, oxidoreductase, pyruvate dehydrogenase complex, alpha-ketoglutarate dehydrogenase complex
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 8
• Total formula weight: 427396.48

Authors

Szabo, E.,Mizsei, R.,Wilk, P.,Zambo, Z.,Torocsik, B.,Weiss, M.S.,Adam-Vizi, V.,Ambrus, A. (deposition date: 2017-03-21, release date: 2018-05-16, Last modification date: 2024-11-13)

Primary citation

Szabo, E.,Mizsei, R.,Wilk, P.,Zambo, Z.,Torocsik, B.,Weiss, M.S.,Adam-Vizi, V.,Ambrus, A.
Crystal structures of the disease-causing D444V mutant and the relevant wild type human dihydrolipoamide dehydrogenase.
Free Radic. Biol. Med., 124:214-220, 2018

PubMed Abstract: We report the crystal structures of the human (dihydro)lipoamide dehydrogenase (hLADH, hE3) and its disease-causing homodimer interface mutant D444V-hE3 at 2.27 and 1.84 Å resolution, respectively. The wild type structure is a unique uncomplexed, unliganded hE3 structure with the true canonical sequence. Based on the structural information a novel molecular pathomechanism is proposed for the impaired catalytic activity and enhanced capacity for reactive oxygen species generation of the pathogenic mutant. The mechanistic model involves a previously much ignored solvent accessible channel leading to the active site that might be perturbed also by other disease-causing homodimer interface substitutions of this enzyme.

PubMed: 29908278
DOI: 10.1016/j.freeradbiomed.2018.06.008

Experimental method

X-RAY DIFFRACTION (2.27 Å)