Structure of D-lactate dehydrogenase from Aquifex aeolicus complexed with NAD(+) and lactic acid (or pyruvate).

The crystal structure of D-lactate dehydrogenase from Aquifex aeolicus (aq_727) was determined to 2.12 A resolution in space group P2(1)2(1)2(1), with unit-cell parameters a = 90.94, b = 94.43, c = 188.85 A. The structure was solved by molecular replacement using the coenzyme-binding domain of Lactobacillus helveticus D-lactate dehydrogenase and contained two homodimers in the asymmetric unit. Each subunit of the homodimer was found to be in a ;closed' conformation with the NADH cofactor bound to the coenzyme-binding domain and with a lactate (or pyruvate) molecule bound at the interdomain active-site cleft.

[1]  Z. Dauter,et al.  How nature deals with stereoisomers. , 1995, Current opinion in structural biology.

[2]  A. Vagin,et al.  MOLREP: an Automated Program for Molecular Replacement , 1997 .

[3]  M. M. Bradford.  A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.

[4]  S. Kochhar,et al.  Evolutionary relationship of NAD(+)-dependent D-lactate dehydrogenase: comparison of primary structure of 2-hydroxy acid dehydrogenases. , 1992, Biochemical and biophysical research communications.

[5]  Jack Snoeyink,et al.  Nucleic Acids Research Advance Access published April 22, 2007 MolProbity: all-atom contacts and structure validation for proteins and nucleic acids , 2007 .

[6]  V. Stoll,et al.  Insights into substrate binding by D-2-ketoacid dehydrogenases from the structure of Lactobacillus pentosus D-lactate dehydrogenase. , 1996, Structure.

[7]  E. Pai,et al.  Distinct Conformation-mediated Functions of an Active Site Loop in the Catalytic Reactions of NAD-dependent D-Lactate Dehydrogenase and Formate Dehydrogenase* , 2005, Journal of Biological Chemistry.

[8]  V S Lamzin,et al.  High resolution structures of holo and apo formate dehydrogenase. , 1995, Journal of molecular biology.

[9]  G. Murshudov,et al.  Refinement of macromolecular structures by the maximum-likelihood method. , 1997, Acta crystallographica. Section D, Biological crystallography.

[10]  Karen Willcox,et al.  Kinetics and kinematics for translational motions in microgravity during parabolic flight. , 2009, Aviation, space, and environmental medicine.

[11]  Victor S Lamzin,et al.  Domain closure, substrate specificity and catalysis of D-lactate dehydrogenase from Lactobacillus bulgaricus. , 2002, Journal of molecular biology.

[12]  J. Thornton,et al.  PROCHECK: a program to check the stereochemical quality of protein structures , 1993 .

[13]  Kevin Cowtan,et al.  research papers Acta Crystallographica Section D Biological , 2005 .

[14]  Z. Otwinowski,et al.  [20] Processing of X-ray diffraction data collected in oscillation mode. , 1997, Methods in enzymology.

[15]  N. Kunishima,et al.  High-throughput crystallization-to-structure pipeline at RIKEN SPring-8 Center , 2008, Journal of Structural and Functional Genomics.