Crystal structure of non-allosteric L-lactate dehydrogenase from Lactobacillus pentosus at 2.3 A resolution: specific interactions at subunit interfaces.
L-Lactate dehydrogenase (LDH) from Lactobacillus pentosus is a non-allosteric enzyme, which shows, however, high sequence similarity to allosteric LDHs from certain bacteria. To elucidate the structural basis of the absence of allostery of L. pentosus LDH (LPLDH), we determined the crystal structure of LPLDH at 2.3 A resolution. Bacterial LDHs are tetrameric enzymes composed of identical subunits and exhibit 222 symmetry. The quaternary structure of LPLDH was similar to the active conformation of allosteric LDHs. Structural analysis revealed that the subunit interfaces of LPLDH are optimized mainly through hydrophilic interactions rather than hydrophobic interactions, compared with other LDHs. The subunit interfaces of LPLDH are more specifically stabilized by increased numbers of intersubunit salt bridges and hydrogen bonds, and higher geometrical complementarity. Such high specificity at the subunit interfaces should hinder the rearrangement of the quaternary structure needed for allosteric regulation and thus explain the "non-allostery" of LPLDH.
Uchikoba
Hiroyuki
H
Department of Biotechnology, The University of Tokyo, Tokyo, Japan.
Fushinobu
Shinya
S
Wakagi
Takayoshi
T
Konno
Michiko
M
Taguchi
Hayao
H
Matsuzawa
Hiroshi
H
D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D007770:L-Lactate Dehydrogenase / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D042844:L-Lactate Dehydrogenase (Cytochrome); D007778:Lactobacillus / Q000201:enzymology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits
D021122:Protein Subunits; D007770:L-Lactate Dehydrogenase; D042844:L-Lactate Dehydrogenase (Cytochrome)