Crystal structure of tabtoxin resistance protein complexed with acetyl coenzyme A reveals the mechanism for beta-lactam acetylation.
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.
He
Hongzhen
H
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.
Ding
Yi
Y
Bartlam
Mark
M
Sun
Fei
F
Le
Yi
Y
Qin
Xincheng
X
Tang
Hong
H
Zhang
Rongguang
R
Joachimiak
Andrzej
A
Liu
Jinyuan
J
Zhao
Nanming
N
Rao
Zihe
Z
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
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