Motion in Lactate Dehydrogenase (LDH) [ldh]

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Classification Known Fragment Motion, Hinge Mechanism [F-h-2]

Structures
1LDM Conformation 2 [ PartsList ]
6LDH Conformation 1 [ PartsList ]

Description
Loop closure with 2 hinges, one in helix, moves CA atoms ~11 Angstrom. Upon binding lactate and NAD, lactate dehydrogenase undergoes a large conformational change that results in a surface loop moving roughly 10 A to cover the active site. In addition, there are appreciable movements (approximately 2 A) of five helices and three other loops. The loop moves on two hinges separated by a relatively rigid type II turn. The first hinge has few steric constraints on it, and its motion can be well accounted for by large changes in two torsion angles, i.e. as in a classic hinge motion. In contrast, the second hinge, which is part of a helix connected to the end of the loop, has many more constraints on it and distributes its deformation over more torsion angles. This novel motion involves the helix stretching and splitting into alpha-helical and 3(10)-helical components and substantial side-chain repacking in the sense of 'cogs hopping between grooves' at its interface with the end of a neighboring helix. The loop is stabilized by five transverse (across loop) hydrogen bonds. These are preserved, through the conformational change and through 17 lactate dehydrogenase sequences, more than the longitudinal hydrogen bonds down the sides of the loop. Through a network of contacts, many of them conserved hydrophobic residues, the motion of the loop is propagated outward to structures that have no direct contact with the ligands. These moving structures are on the surface of the protein, and the whole protein can be subdivided into concentric shells of increasing mobility.

Particular values describing motion
Experimental Methods = x (Traditional x-ray)
Creation Date = 19970822
Modification Date = 19970822

References
S Iwata, K Kamata, S Yoshida, T Minowa, and T Ohta (1994). T and R states in the crystals of bacterial L-lactate dehydrogenase reveal the mechanism for allosteric control. Struct. biol. 1:176. [Medline info for 93266593]
J White, M L Hackert, M Buehner, M J Adams, G C Ford, P J J Lentz, I E Smiley, S J Steindel and M G Rossman (1976). A Comparison of the Structures of Apo Dogfish M4 Lactate Dehydrogenase and Its Ternary Complexes. J. Mol. Biol. 102: 759-79. [Medline info for 93266593]
M Gerstein and C H Chothia (1991). Analysis of Protein Loop Closure: Two Types of Hinges Produce One Motion in Lactate Dehydrogenase. J. Mol. Biol. 220: 133-149. [Medline info for 91295198]

Data and Graphics
Graphic-2 Closeup of loop motion.
Graphic-3 Closeup of second hinge: alpha helix stretching into 3-10 helix.
Graphic-1 Overall picture of loop motion.

GO terms associated with structures
Molecular functionoxidoreductase activity, L-lactate dehydrogenase activity
Cellular componentcytoplasm
Biological processanaerobic glycolysis, glycolysis, tricarboxylic acid cycle intermediate metabolism

Morphs

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Best representative
Morph Morph name Structure #1 Structure #2 Residues
LDH (B. stearothermophilus) 6ldh [ A ] 1ldm [ A ] 329

User-submitted morphs
Morph Morph name Structure #1 Structure #2 Residues
70250-17914 Lactate dehydrogenase 1ldm [ ] 6ldh [ ] 329
379021-6800 lactate dehydrogenase-2 upload [ A ] upload [ A ] 329
425484-23987 Lactate DH 6ldh [ A ] 1ldm [ A ] 329
347379-24714 LDH (B. stearothermophilus) 1ldb [ A ] 1ldn [ A ] 316
347462-24750 LDH (B. stearothermophilus) 1ldb [ A ] 2ldb [ A ] 317
347300-24661 LDH (L. bulgaricus) 1j4a [ A ] 1j49 [ A ] 333
010422-11461 Pig Heart Lactate Dehydrogenase 9ldb [ A ] 9ldt [ A ] 331


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Copyright 1995-2005 M. Gerstein, W. Krebs, S. Flores, N. Echols, and others
Email: Mark.Gerstein _at_ yale.edu