PDBsum entry 1e2t

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protein Protein-protein interface(s) links
Transferase PDB id
Protein chains
(+ 2 more) 274 a.a. *
Waters ×468
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Arylamine n-acetyltransferase (nat) from salmonella typhimurium
Structure: N-hydroxyarylamine o-acetyltransferase. Chain: a, b, c, d, e, f, g, h. Synonym: nat. Engineered: yes
Source: Salmonella typhimurium. Organism_taxid: 602. Gene: nhoa. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PDB file)
2.80Å     R-factor:   0.264     R-free:   0.302
Authors: J.C.Sinclair,J.Sandy,R.Delgoda,E.Sim,M.E.M.Noble
Key ref:
J.C.Sinclair et al. (2000). Structure of arylamine N-acetyltransferase reveals a catalytic triad. Nat Struct Biol, 7, 560-564. PubMed id: 10876241 DOI: 10.1038/76783
24-May-00     Release date:   07-Jul-00    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q00267  (NHOA_SALTY) -  N-hydroxyarylamine O-acetyltransferase
281 a.a.
274 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - N-hydroxyarylamine O-acetyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Acetyl-CoA + an N-hydroxyarylamine = CoA + an N-acetoxyarylamine
+ N-hydroxyarylamine
= CoA
+ N-acetoxyarylamine
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   1 term 
  Biochemical function     transferase activity     4 terms  


    Added reference    
DOI no: 10.1038/76783 Nat Struct Biol 7:560-564 (2000)
PubMed id: 10876241  
Structure of arylamine N-acetyltransferase reveals a catalytic triad.
J.C.Sinclair, J.Sandy, R.Delgoda, E.Sim, M.E.Noble.
Enzymes of the arylamine N-acetyltransferase (NAT) family are found in species ranging from Escherichia coli to humans. In humans they are known to be responsible for the acetylation of a number of arylamine and hydrazine drugs, and they are strongly linked to the carcinogenic potentiation of certain foreign substances. In prokaryotes their substrate specificities may vary and members of the gene family have been linked to pathways including amide synthesis during rifamycin production. Here we report the crystal structure at 2.8 A resolution of a representative member of this family from Salmonella typhimurium in the presence and absence of a covalently bound product analog. The structure reveals surprising mechanistic information including the presence of a Cys-His-Asp catalytic triad. The fold can be described in terms of three domains of roughly equal length with the second and third domains linked by an interdomain helix. The first two domains, a helical bundle and a beta-barrel, make up the catalytic triad using a structural motif identical to that of the cysteine protease superfamily.
  Selected figure(s)  
Figure 3.
Figure 3. Structural homologs of NAT. a, Structural alignment of the cysteine protease motif of NAT with that of staphopain (PDB code 1CV8). Residues 68 -137 of NAT (red) and residues 23 -37 and 101 -150 of staphopain (blue) are shown with a least squares alignment of C atoms. The catalytic triads of NAT (yellow) and staphopain (green) are also indicated. Purple spheres mark the position of backbone amide nitrogens within the putative phosphate binding P-loop of the NAT structure. b, Structural alignment of NAT with the catalytic core of factor XIII transglutaminase (PDB code 1F13). Residues 3 -140 of NAT (red) and residues 226 -345 and 361 -418 of transglutaminase (blue) are shown with a least squares alignment of C atoms. The catalytic triads of NAT (yellow) and transglutaminase (green) are also indicated.
Figure 4.
Figure 4. The active site of NAT with bound p-bromoacetanilide inhibitor. a, Stereo view showing residues that interact with the bound p-bromoacetanilide product analog. Residues forming part of the binding pocket are shown in ball-and-stick representation, colored according to domain as in Fig. 2b. An anomalous difference Fourier is shown contoured at 6 (red). This clearly identifies the position of the bromine in the product analog. b, The position of the product analog within the active site cleft. Regions are colored according to domain as in Fig. 2b.
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2000, 7, 560-564) copyright 2000.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
23151626 S.S.Bhaskaran, and C.E.Stebbins (2012).
Structure of the catalytic domain of the Salmonella virulence factor SseI.
  Acta Crystallogr D Biol Crystallogr, 68, 1613-1621.
PDB codes: 4g29 4g2b
21347396 J.M.Tiang, N.J.Butcher, C.Cullinane, P.O.Humbert, and R.F.Minchin (2011).
RNAi-Mediated Knock-Down of Arylamine N-acetyltransferase-1 Expression Induces E-cadherin Up-Regulation and Cell-Cell Contact Growth Inhibition.
  PLoS One, 6, e17031.  
20722598 B.A.Wilson, and M.Ho (2010).
Recent insights into Pasteurella multocida toxin and other G-protein-modulating bacterial toxins.
  Future Microbiol, 5, 1185-1201.  
20176657 N.J.Butcher, and R.F.Minchin (2010).
Arylamine N-acetyltransferase 1 gene regulation by androgens requires a conserved heat shock element for heat shock factor-1.
  Carcinogenesis, 31, 820-826.  
19302487 A.E.Glenn, and C.W.Bacon (2009).
FDB2 encodes a member of the arylamine N-acetyltransferase family and is necessary for biotransformation of benzoxazolinones by Fusarium verticillioides.
  J Appl Microbiol, 107, 657-671.  
19782440 A.Mirza, R.Desai, and J.Reynisson (2009).
Known drug space as a metric in exploring the boundaries of drug-like chemical space.
  Eur J Med Chem, 44, 5006-5011.  
19379125 D.W.Hein (2009).
N-acetyltransferase SNPs: emerging concepts serve as a paradigm for understanding complexities of personalized medicine.
  Expert Opin Drug Metab Toxicol, 5, 353-366.  
19636684 E.Fullam, A.Kawamura, H.Wilkinson, A.Abuhammad, I.Westwood, and E.Sim (2009).
Comparison of the Arylamine N-acetyltransferase from Mycobacterium marinum and Mycobacterium tuberculosis.
  Protein J, 28, 281-293.  
19463782 N.Zhang, and K.J.Walters (2009).
Insights into how protein dynamics affects arylamine N-acetyltransferase catalysis.
  Biochem Biophys Res Commun, 385, 395-401.  
19860825 X.Zhou, N.Zhang, L.Liu, K.J.Walters, P.E.Hanna, and C.R.Wagner (2009).
Probing the catalytic potential of the hamster arylamine N-acetyltransferase 2 catalytic triad by site-directed mutagenesis of the proximal conserved residue, Tyr190.
  FEBS J, 276, 6928-6941.  
18280460 A.Kawamura, I.Westwood, L.Wakefield, H.Long, N.Zhang, K.Walters, C.Redfield, and E.Sim (2008).
Mouse N-acetyltransferase type 2, the homologue of human N-acetyltransferase type 1.
  Biochem Pharmacol, 75, 1550-1560.  
18795795 A.L.Sikora, B.A.Frankel, and J.S.Blanchard (2008).
Kinetic and chemical mechanism of arylamine N-acetyltransferase from Mycobacterium tuberculosis.
  Biochemistry, 47, 10781-10789.  
18184660 D.Shi, V.Sagar, Z.Jin, X.Yu, L.Caldovic, H.Morizono, N.M.Allewell, and M.Tuchman (2008).
The crystal structure of N-acetyl-L-glutamate synthase from Neisseria gonorrhoeae provides insights into mechanisms of catalysis and regulation.
  J Biol Chem, 283, 7176-7184.
PDB codes: 2r8v 2r98 3b8g
18680471 E.Sim, J.Sandy, D.Evangelopoulos, E.Fullam, S.Bhakta, I.Westwood, A.Krylova, N.Lack, and M.Noble (2008).
Arylamine N-acetyltransferases in mycobacteria.
  Curr Drug Metab, 9, 510-519.  
18259988 J.M.Walraven, J.O.Trent, and D.W.Hein (2008).
Structure-function analyses of single nucleotide polymorphisms in human N-acetyltransferase 1.
  Drug Metab Rev, 40, 169-184.  
18680467 J.M.Walraven, Y.Zang, J.O.Trent, and D.W.Hein (2008).
Structure/function evaluations of single nucleotide polymorphisms in human N-acetyltransferase 2.
  Curr Drug Metab, 9, 471-486.  
18709443 J.R.Cort, T.A.Ramelot, D.Murray, T.B.Acton, L.C.Ma, R.Xiao, G.T.Montelione, and M.A.Kennedy (2008).
Structure of an acetyl-CoA binding protein from Staphylococcus aureus representing a novel subfamily of GCN5-related N-acetyltransferase-like proteins.
  J Struct Funct Genomics, 9, 7.
PDB codes: 1r57 2h5m
19018723 L.A.Stanley, and E.Sim (2008).
Update on the pharmacogenetics of NATs: structural considerations.
  Pharmacogenomics, 9, 1673-1693.  
  18763302 Y.B.Ji, and S.Y.Gao (2008).
Arylamine N-acetyltransferases: a new inhibitor of apoptosis in HepG2 cells.
  J Zhejiang Univ Sci B, 9, 701-706.  
18845161 Y.Hsu, G.Jubelin, F.Taieb, J.P.Nougayrède, E.Oswald, and C.E.Stebbins (2008).
Structure of the cyclomodulin Cif from pathogenic Escherichia coli.
  J Mol Biol, 384, 465-477.
PDB code: 3efy
  17909290 B.Pluvinage, la Sierra-Gallay, M.Martins, N.Ragunathan, J.M.Dupret, and F.Rodrigues-Lima (2007).
Crystallization and preliminary X-ray characterization of arylamine N-acetyltransferase C (BanatC) from Bacillus anthracis.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 862-864.  
17428149 E.Sim, I.Westwood, and E.Fullam (2007).
Arylamine N-acetyltransferases.
  Expert Opin Drug Metab Toxicol, 3, 169-184.  
17158669 H.Suzuki, Y.Ohnishi, and S.Horinouchi (2007).
Arylamine N-acetyltransferase responsible for acetylation of 2-aminophenols in Streptomyces griseus.
  J Bacteriol, 189, 2155-2159.  
17656365 H.Wu, L.Dombrovsky, W.Tempel, F.Martin, P.Loppnau, G.H.Goodfellow, D.M.Grant, and A.N.Plotnikov (2007).
Structural basis of substrate-binding specificity of human arylamine N-acetyltransferases.
  J Biol Chem, 282, 30189-30197.
PDB code: 2pqt
17374145 I.M.Westwood, and E.Sim (2007).
Kinetic characterisation of arylamine N-acetyltransferase from Pseudomonas aeruginosa.
  BMC Biochem, 8, 3.  
17371801 J.M.Walraven, J.O.Trent, and D.W.Hein (2007).
Computational and experimental analyses of mammalian arylamine N-acetyltransferase structure and function.
  Drug Metab Dispos, 35, 1001-1007.  
18033585 J.Stöckigt, and S.Panjikar (2007).
Structural biology in plant natural product biosynthesis--architecture of enzymes from monoterpenoid indole and tropane alkaloid biosynthesis.
  Nat Prod Rep, 24, 1382-1400.  
17360394 K.Kitadokoro, S.Kamitani, M.Miyazawa, M.Hanajima-Ozawa, A.Fukui, M.Miyake, and Y.Horiguchi (2007).
Crystal structures reveal a thiol protease-like catalytic triad in the C-terminal region of Pasteurella multocida toxin.
  Proc Natl Acad Sci U S A, 104, 5139-5144.
PDB codes: 2ebf 2ebh 2ec5
17392017 R.F.Minchin, P.E.Hanna, J.M.Dupret, C.R.Wagner, F.Rodrigues-Lima, and N.J.Butcher (2007).
Arylamine N-acetyltransferase I.
  Int J Biochem Cell Biol, 39, 1999-2005.  
17264801 Y.Zang, S.Zhao, M.A.Doll, J.Christopher States, and D.W.Hein (2007).
Functional characterization of the A411T (L137F) and G364A (D122N) genetic polymorphisms in human N-acetyltransferase 2.
  Pharmacogenet Genomics, 17, 37-45.  
16550165 D.W.Hein (2006).
N-acetyltransferase 2 genetic polymorphism: effects of carcinogen and haplotype on urinary bladder cancer risk.
  Oncogene, 25, 1649-1658.  
16573698 F.Rodrigues-Lima, J.Dairou, C.L.Diaz, M.C.Rubio, E.Sim, H.P.Spaink, and J.M.Dupret (2006).
Cloning, functional expression and characterization of Mesorhizobium loti arylamine N-acetyltransferases: rhizobial symbiosis supplies leguminous plants with the xenobiotic N-acetylation pathway.
  Mol Microbiol, 60, 505-512.  
16500903 G.Zhao, X.Zhou, L.Wang, G.Li, C.Kisker, W.J.Lennarz, and H.Schindelin (2006).
Structure of the mouse peptide N-glycanase-HR23 complex suggests co-evolution of the endoplasmic reticulum-associated degradation and DNA repair pathways.
  J Biol Chem, 281, 13751-13761.
PDB codes: 2f4m 2f4o
16003948 H.Wang, G.M.Vath, A.Kawamura, C.A.Bates, E.Sim, P.E.Hanna, and C.R.Wagner (2005).
Over-expression, purification, and characterization of recombinant human arylamine N-acetyltransferase 1.
  Protein J, 24, 65-77.  
15964983 J.H.Lee, J.M.Choi, C.Lee, K.J.Yi, and Y.Cho (2005).
Structure of a peptide:N-glycanase-Rad23 complex: insight into the deglycosylation for denatured glycoproteins.
  Proc Natl Acad Sci U S A, 102, 9144-9149.
PDB codes: 1x3w 1x3z
  16508079 S.J.Holton, J.Dairou, J.Sandy, F.Rodrigues-Lima, J.M.Dupret, M.E.Noble, and E.Sim (2005).
Structure of Mesorhizobium loti arylamine N-acetyltransferase 1.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 61, 14-16.
PDB code: 2bsz
14672957 J.Dairou, N.Atmane, F.Rodrigues-Lima, and J.M.Dupret (2004).
Peroxynitrite irreversibly inactivates the human xenobiotic-metabolizing enzyme arylamine N-acetyltransferase 1 (NAT1) in human breast cancer cells: a cellular and mechanistic study.
  J Biol Chem, 279, 7708-7714.  
15288868 K.Ginalski, L.Kinch, L.Rychlewski, and N.V.Grishin (2004).
BTLCP proteins: a novel family of bacterial transglutaminase-like cysteine proteinases.
  Trends Biochem Sci, 29, 392-395.  
15039438 N.J.Butcher, A.Arulpragasam, and R.F.Minchin (2004).
Proteasomal degradation of N-acetyltransferase 1 is prevented by acetylation of the active site cysteine: a mechanism for the slow acetylator phenotype and substrate-dependent down-regulation.
  J Biol Chem, 279, 22131-22137.  
12832400 N.Atmane, J.Dairou, A.Paul, J.M.Dupret, and F.Rodrigues-Lima (2003).
Redox regulation of the human xenobiotic metabolizing enzyme arylamine N-acetyltransferase 1 (NAT1). Reversible inactivation by hydrogen peroxide.
  J Biol Chem, 278, 35086-35092.  
12620121 V.Anantharaman, and L.Aravind (2003).
Evolutionary history, structural features and biochemical diversity of the NlpC/P60 superfamily of enzymes.
  Genome Biol, 4, R11.  
11966400 F.Pompeo, E.Brooke, A.Kawamura, A.Mushtaq, and E.Sim (2002).
The pharmacogenetics of NAT: structural aspects.
  Pharmacogenomics, 3, 19-30.  
12222687 P.D.Josephy, J.Summerscales, L.S.DeBruin, C.Schlaeger, and J.Ho (2002).
N-hydroxyarylamine O-acetyltransferase-deficient Escherichia coli strains are resistant to the mutagenicity of nitro compounds.
  Biol Chem, 383, 977-982.  
12142728 S.Boukouvala, N.Price, and E.Sim (2002).
Identification and functional characterization of novel polymorphisms associated with the genes for arylamine N-acetyltransferases in mice.
  Pharmacogenetics, 12, 385-394.  
12222688 Y.Zhu, M.A.Doll, and D.W.Hein (2002).
Functional genomics of C190T single nucleotide polymorphism in human N-acetyltransferase 2.
  Biol Chem, 383, 983-987.  
11703656 A.M.Upton, A.Mushtaq, T.C.Victor, S.L.Sampson, J.Sandy, D.M.Smith, P.V.van Helden, and E.Sim (2001).
Arylamine N-acetyltransferase of Mycobacterium tuberculosis is a polymorphic enzyme and a site of isoniazid metabolism.
  Mol Microbiol, 42, 309-317.  
11239577 A.Upton, N.Johnson, J.Sandy, and E.Sim (2001).
Arylamine N-acetyltransferases - of mice, men and microorganisms.
  Trends Pharmacol Sci, 22, 140-146.  
11344150 C.Deloménie, S.Fouix, S.Longuemaux, N.Brahimi, C.Bizet, B.Picard, E.Denamur, and J.M.Dupret (2001).
Identification and functional characterization of arylamine N-acetyltransferases in eubacteria: evidence for highly selective acetylation of 5-aminosalicylic acid.
  J Bacteriol, 183, 3417-3427.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.