title: Crystal structure of the homocysteine methyltransferase MmuM from Escherichia coli.
abstract: Homocysteine S-methyltransferases (HMTs, EC 2.1.1.0) catalyse the conversion of homocysteine to methionine using S-methylmethionine or S-adenosylmethionine as the methyl donor. HMTs play an important role in methionine biosynthesis and are widely distributed among micro-organisms, plants and animals. Additionally, HMTs play a role in metabolite repair of S-adenosylmethionine by removing an inactive diastereomer from the pool. The mmuM gene product from Escherichia coli is an archetypal HMT family protein and contains a predicted zinc-binding motif in the enzyme active site. In the present study, we demonstrate X-ray structures for MmuM in oxidized, apo and metallated forms, representing the first such structures for any member of the HMT family. The structures reveal a metal/substrate-binding pocket distinct from those in related enzymes. The presented structure analysis and modelling of co-substrate interactions provide valuable insight into the function of MmuM in both methionine biosynthesis and cofactor repair.
authors.affiliation: Department of Chemistry, University of Florida, Gainesville, FL 32611, U.S.A.
authors.forename: Kunhua
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Chemistry, University of Florida, Gainesville, FL 32611, U.S.A.
authors.forename: Gengnan
authors.initials: G
authors.lastname: Li
authors.affiliation: Horticultural Sciences Department, University of Florida, Gainesville, FL 32611, U.S.A.
authors.forename: Louis M T
authors.initials: LM
authors.lastname: Bradbury
authors.affiliation: Horticultural Sciences Department, University of Florida, Gainesville, FL 32611, U.S.A.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Hanson
authors.affiliation: Department of Chemistry, University of Florida, Gainesville, FL 32611, U.S.A. bruner@ufl.edu.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Bruner
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006710:Homocysteine / Q000378:metabolism; D050904:Homocysteine S-Methyltransferase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008715:Methionine / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016415:Sequence Alignment
chemical_list: D029968:Escherichia coli Proteins; D006710:Homocysteine; D008715:Methionine; D050904:Homocysteine S-Methyltransferase; C494408:mmuM protein, E coli
keywords: S-methylmethionine; adenosylmethionine; homocysteine S-methyl-transferase; metabolite damage; metabolite repair; methionine biosynthesis