title: The structure of dihydrodipicolinate reductase (DapB) from Mycobacterium tuberculosis in three crystal forms.
abstract: Dihydrodipicolinate reductase (DHDPR, DapB) is an enzyme that belongs to the L-lysine biosynthetic pathway. DHDPR reduces the alpha,beta-unsaturated cyclic imine 2,3-dihydrodipicolinic acid to yield the compound 2,3,4,5-tetrahydrodipicolinic acid in a pyridine nucleotide-dependent reaction. The substrate of this reaction is the unstable product of the preceding enzyme dihydrodipicolinate synthase (DHDPS, DapA). Here, the structure of apo-DHDPR from Mycobacterium tuberculosis is reported in two orthorhombic crystal forms, as well as the structure of DHDPR from M. tuberculosis in complex with NADH in a monoclinic crystal form. A comparison of the results with previously solved structures of this enzyme shows that DHDPR undergoes a major conformational change upon binding of its cofactor. This conformational change can be interpreted as one of the low-frequency normal modes of the structure.
authors.affiliation: EMBL Hamburg Outstation, c/o DESY, Notkestrasse 85, D-22603 Hamburg, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Janowski
authors.forename: Georgia
authors.initials: G
authors.lastname: Kefala
authors.forename: Manfred S
authors.initials: MS
authors.lastname: Weiss
mesh_terms: D000494:Allosteric Regulation; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D003460:Crystallization; D018360:Crystallography, X-Ray; D050746:Dihydrodipicolinate Reductase / Q000737:chemistry* / Q000378:metabolism; D006836:Hydro-Lyases / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D009243:NAD / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D011725:Pyridines / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D011725:Pyridines; D009243:NAD; D050746:Dihydrodipicolinate Reductase; D006836:Hydro-Lyases; C020040:4-hydroxy-tetrahydrodipicolinate synthase; C023666:pyridine