Structural Basis of Sequential Allosteric Transitions in Tetrameric d-Lactate Dehydrogenases from Three Gram-Negative Bacteria
Abstract
d-Lactate dehydrogenases (d-LDHs) from Fusobacterium nucleatum (FnLDH) and Escherichia coli (EcLDH) exhibit positive cooperativity in substrate binding, and the Pseudomonas aeruginosa enzyme (PaLDH) shows negatively cooperative substrate binding. The apo and ternary complex structures of FnLDH and PaLDH have been determined together with the apo-EcLDH structure. The three enzymes consistently form homotetrameric structures with three symmetric axes, the P-, Q-, and R-axes, unlike Lactobacillus d-LDHs, P-axis-related dimeric enzymes, although apo-FnLDH and EcLDH form asymmetric and distorted quaternary structures. The tetrameric structure allows apo-FnLDH and EcLDH to form wide intersubunit contact surfaces between the opened catalytic domains of the two Q-axis-related subunits in coordination with their asymmetric and distorted quaternary structures. These contact surfaces comprise intersubunit hydrogen bonds and hydrophobic interactions and likely prevent the domain closure motion during initial substrate binding. In contrast, apo-PaLDH possesses a highly symmetrical quaternary structure and partially closed catalytic domains that are favorable for initial substrate binding and forms virtually no intersubunit contact surface b...Continue Reading
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