title: Crystal structure of tabtoxin resistance protein complexed with acetyl coenzyme A reveals the mechanism for beta-lactam acetylation.
abstract: Tabtoxin resistance protein (TTR) is an enzyme that renders tabtoxin-producing pathogens, such as Pseudomonas syringae, tolerant to their own phytotoxins. Here, we report the crystal structure of TTR complexed with its natural cofactor, acetyl coenzyme A (AcCoA), to 1.55A resolution. The binary complex forms a characteristic "V" shape for substrate binding and contains the four motifs conserved in the GCN5-related N-acetyltransferase (GNAT) superfamily, which also includes the histone acetyltransferases (HATs). A single-step mechanism is proposed to explain the function of three conserved residues, Glu92, Asp130 and Tyr141, in catalyzing the acetyl group transfer to its substrate. We also report that TTR possesses HAT activity and suggest an evolutionary relationship between TTR and other GNAT members.
authors.affiliation: Laboratory of Structural Biology, and MOE Laboratory of Protein Science, School of Life Sciences and Engineering, Tsinghua University, 100084, Beijing, People's Republic of China.
authors.forename: Hongzhen
authors.initials: H
authors.lastname: He
authors.forename: Yi
authors.initials: Y
authors.lastname: Ding
authors.forename: Mark
authors.initials: M
authors.lastname: Bartlam
authors.forename: Fei
authors.initials: F
authors.lastname: Sun
authors.forename: Yi
authors.initials: Y
authors.lastname: Le
authors.forename: Xincheng
authors.initials: X
authors.lastname: Qin
authors.forename: Hong
authors.initials: H
authors.lastname: Tang
authors.forename: Rongguang
authors.initials: R
authors.lastname: Zhang
authors.forename: Andrzej
authors.initials: A
authors.lastname: Joachimiak
authors.forename: Jinyuan
authors.initials: J
authors.lastname: Liu
authors.forename: Nanming
authors.initials: N
authors.lastname: Zhao
authors.forename: Zihe
authors.initials: Z
authors.lastname: Rao
mesh_terms: D000105:Acetyl Coenzyme A / Q000737:chemistry* / Q000378:metabolism; D000107:Acetylation; D000123:Acetyltransferases / Q000737:chemistry* / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001426:Bacterial Proteins; D003460:Crystallization; D018360:Crystallography, X-Ray; D029721:Drosophila Proteins; D051548:Histone Acetyltransferases; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D011487:Protein Conformation; D011549:Pseudomonas / Q000201:enzymology*; D011994:Recombinant Proteins / Q000737:chemistry; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism; D012645:Selenomethionine / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D047090:beta-Lactams / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D000105:Acetyl Coenzyme A; D000123:Acetyltransferases; D001426:Bacterial Proteins; D029721:Drosophila Proteins; D051548:Histone Acetyltransferases; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D012645:Selenomethionine; D047090:beta-Lactams; C441636:tabtoxin-resistance protein, Pseudomonas syringae; C470557:GCN5 protein, Drosophila; D000099224:p300-CBP-Associated Factor