How a protein binds B12: A 3.0 A X-ray structure of B12-binding domains of methionine synthase.
The crystal structure of a 27-kilodalton methylcobalamin-containing fragment of methionine synthase from Escherichia coli was determined at 3.0 A resolution. This structure depicts cobalamin-protein interactions and reveals that the corrin macrocycle lies between a helical amino-terminal domain and an alpha/beta carboxyl-terminal domain that is a variant of the Rossmann fold. Methylcobalamin undergoes a conformational change on binding the protein; the dimethylbenzimidazole group, which is coordinated to the cobalt in the free cofactor, moves away from the corrin and is replaced by a histidine contributed by the protein. The sequence Asp-X-His-X-X-Gly, which contains this histidine ligand, is conserved in the adenosylcobalamin-dependent enzymes methylmalonyl-coenzyme A mutase and glutamate mutase, suggesting that displacement of the dimethylbenzimidazole will be a feature common to many cobalamin-binding proteins. Thus the cobalt ligand, His759, and the neighboring residues Asp757 and Ser810, may form a catalytic quartet, Co-His-Asp-Ser, that modulates the reactivity of the B12 prosthetic group in methionine synthase.
Drennan
C L
CL
Biophysics Research Division, University of Michigan, Ann Arbor 48109-1055.
Huang
S
S
Drummond
J T
JT
Matthews
R G
RG
Ludwig
M L
ML
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000737:chemistry* / Q000378:metabolism; D000591:Amino Acid Isomerases / Q000737:chemistry; D000595:Amino Acid Sequence; D001562:Benzimidazoles; D002384:Catalysis; D003196:Computer Graphics; D018360:Crystallography, X-Ray; D004578:Electron Spin Resonance Spectroscopy; D004926:Escherichia coli / Q000201:enzymology*; D006639:Histidine / Q000378:metabolism; D019751:Intramolecular Transferases; D008024:Ligands; D008745:Methylation; D008765:Methylmalonyl-CoA Mutase / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D014805:Vitamin B 12 / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism
D001562:Benzimidazoles; D008024:Ligands; D006639:Histidine; C019476:mecobalamin; D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D000591:Amino Acid Isomerases; D019751:Intramolecular Transferases; C021570:methylaspartate mutase; D008765:Methylmalonyl-CoA Mutase; D014805:Vitamin B 12