The crystal structure of d- lactate dehydrogenase, a peripheral membrane respiratory enzyme

An Unconventional Hexacoordinated Flavohemoglobin from Mycobacterium tuberculosis

“…This study shows that MtbFHb is a peripheral membraneassociated protein that catalyzes the oxidation of D-lactate into pyruvate in a FAD-dependent manner, similar to the respiratory (NAD-independent) D-LDHs (32). Because M. tuberculosis lacks a D-lactate-metabolizing gene, the accumulation of D-lactate under oxidative stress as a byproduct of lipid peroxidation may be highly toxic to the cell due to increased OH ⅐ generation.…”

“…The electron transfer function of MtbFHb is supported by the observation that the addition of D-lactate to MtbFHb, but not the heme domain alone, changes the heme iron from the Fe 3ϩ to Fe 2ϩ state. Respiratory FAD-dependent D-LDH is known to be a peripheral membrane protein that participates in electron transfer (32); such a role for MtbFHb may be envisioned due to its close proximity with the respiratory membrane. This is supported by the observation that the transcriptional activity of Rv0385 increases significantly in the presence of bicyclic nitroimidazoles like PA-824 that mainly affect genes involved in cell wall biogenesis and respiration (49).…”

“…The lack of a conserved lysine residue at F7 within the globin domain and the glutamine residue at 394 position of the reductase domain, required for the electron transfer from reductase to globin domain in conventional FHbs (9), suggests that the interactions between the globin and reductase domains in MtbFHb may be different. Although the conserved FAD binding site is mutated in MtbFHb, two sequence motifs, AX 8 AXN and GX 7 GS, which are similar to the FAD binding motifs (AX 7 AXN and GX 7 GS) of the respiratory D-LDHs (22,32), overlap with the mutated NADH binding site (Fig. 1A).…”

Precursor of ether phospholipids is synthesized by a flavoenzyme through covalent catalysis

“…Another related observation is the recurrent presence in alcohol dehydrogenases of a His residue located with respect to the flavin as His617 of ADPS (26) (Fig. S5).…”

Bioenergetics and Biological Electron Transport

“…As an example, Figure 1.16 shows an electron transport chain for Escherichia coli during anaerobic respiration [46,47]. In this case, nitrate replaces oxygen as the ultimate electron acceptor.…”