title: METALLOPROTEINS. A tethered niacin-derived pincer complex with a nickel-carbon bond in lactate racemase.
abstract: Lactic acid racemization is involved in lactate metabolism and cell wall assembly of many microorganisms. Lactate racemase (Lar) requires nickel, but the nickel-binding site and the role of three accessory proteins required for its activation remain enigmatic. We combined mass spectrometry and x-ray crystallography to show that Lar from Lactobacillus plantarum possesses an organometallic nickel-containing prosthetic group. A nicotinic acid mononucleotide derivative is tethered to Lys(184) and forms a tridentate pincer complex that coordinates nickel through one metal-carbon and two metal-sulfur bonds, with His(200) as another ligand. Although similar complexes have been previously synthesized, there was no prior evidence for the existence of pincer cofactors in enzymes. The wide distribution of the accessory proteins without Lar suggests that it may play a role in other enzymes.
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Benoît
authors.initials: B
authors.lastname: Desguin
authors.affiliation: Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Tuo
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Institute of Life Sciences, Université Catholique de Louvain, B-1348 Louvain-la-Neuve, Belgium.
authors.forename: Patrice
authors.initials: P
authors.lastname: Soumillion
authors.affiliation: Institute of Life Sciences, Université Catholique de Louvain, B-1348 Louvain-la-Neuve, Belgium.
authors.forename: Pascal
authors.initials: P
authors.lastname: Hols
authors.affiliation: Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA. Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA. hujian1@msu.edu hausinge@msu.edu.
authors.forename: Jian
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, USA. Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA. hujian1@msu.edu hausinge@msu.edu.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Hausinger
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D001665:Binding Sites; D002244:Carbon / Q000737:chemistry; D002384:Catalysis; D018360:Crystallography, X-Ray; D006639:Histidine / Q000737:chemistry; D020035:Holoenzymes / Q000737:chemistry; D019344:Lactic Acid / Q000096:biosynthesis* / Q000737:chemistry; D048191:Lactiplantibacillus plantarum / Q000201:enzymology* / Q000235:genetics; D008024:Ligands; D008239:Lysine / Q000737:chemistry; D008667:Metalloproteins / Q000737:chemistry* / Q000235:genetics; D009525:Niacin / Q000737:chemistry*; D009532:Nickel / Q000737:chemistry*; D009537:Nicotinamide Mononucleotide / Q000031:analogs & derivatives / Q000737:chemistry; D011499:Protein Processing, Post-Translational; D017433:Protein Structure, Secondary; D019998:Racemases and Epimerases / Q000737:chemistry* / Q000235:genetics; D021241:Spectrometry, Mass, Electrospray Ionization; D013455:Sulfur
chemical_list: D001426:Bacterial Proteins; D020035:Holoenzymes; D008024:Ligands; D008667:Metalloproteins; D009537:Nicotinamide Mononucleotide; D009525:Niacin; C002953:nicotinate mononucleotide; D019344:Lactic Acid; D006639:Histidine; D013455:Sulfur; D002244:Carbon; D009532:Nickel; D019998:Racemases and Epimerases; C021498:lactate racemase; D008239:Lysine