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PDBsum entry 1gx3

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protein Protein-protein interface(s) links
Transferase PDB id
1gx3
Jmol
Contents
Protein chains
276 a.a. *
Waters ×755
* Residue conservation analysis
PDB id:
1gx3
Name: Transferase
Title: M. Smegmatis arylamine n-acetyl transferase
Structure: Arylamine n-acetyltransferase. Chain: a, b, c, d. Synonym: n-hydroxyarylamine o-acetyltransferase. Engineered: yes. Other_details: (his)6 and 3 residues introduced before authentic starting methionine as cloning artefacts
Source: Mycobacterium smegmatis. Organism_taxid: 1772. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: plyss.
Resolution:
1.70Å     R-factor:   0.211     R-free:   0.241
Authors: J.Sandy,A.Mushtaq,A.Kawamura,J.Sinclair,E.Sim,M.Noble
Key ref:
J.Sandy et al. (2002). The structure of arylamine N-acetyltransferase from Mycobacterium smegmatis--an enzyme which inactivates the anti-tubercular drug, isoniazid. J Mol Biol, 318, 1071-1083. PubMed id: 12054803 DOI: 10.1016/S0022-2836(02)00141-9
Date:
26-Mar-02     Release date:   13-Jun-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
O86309  (NAT_MYCSM) -  Arylamine N-acetyltransferase
Seq:
Struc:
275 a.a.
276 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.3.1.5  - Arylamine N-acetyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Acetyl-CoA + an arylamine = CoA + an N-acetylarylamine
Acetyl-CoA
+ arylamine
= CoA
+ N-acetylarylamine
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     metabolic process   1 term 
  Biochemical function     transferase activity     4 terms  

 

 
    reference    
 
 
DOI no: 10.1016/S0022-2836(02)00141-9 J Mol Biol 318:1071-1083 (2002)
PubMed id: 12054803  
 
 
The structure of arylamine N-acetyltransferase from Mycobacterium smegmatis--an enzyme which inactivates the anti-tubercular drug, isoniazid.
J.Sandy, A.Mushtaq, A.Kawamura, J.Sinclair, E.Sim, M.Noble.
 
  ABSTRACT  
 
Arylamine N-acetyltransferases which acetylate and inactivate isoniazid, an anti-tubercular drug, are found in mycobacteria including Mycobacterium smegmatis and Mycobacterium tuberculosis. We have solved the structure of arylamine N-acetyltransferase from M. smegmatis at a resolution of 1.7 A as a model for the highly homologous NAT from M. tuberculosis. The fold closely resembles that of NAT from Salmonella typhimurium, with a common catalytic triad and domain structure that is similar to certain cysteine proteases. The detailed geometry of the catalytic triad is typical of enzymes which use primary alcohols or thiols as activated nucleophiles. Thermal mobility and structural variations identify parts of NAT which might undergo conformational changes during catalysis. Sequence conservation among eubacterial NATs is restricted to structural residues of the protein core, as well as the active site and a hinge that connects the first two domains of the NAT structure. The structure of M. smegmatis NAT provides a template for modelling the structure of the M. tuberculosis enzyme and for structure-based ligand design as an approach to designing anti-TB drugs.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. Domain orientation comparison between S. typhimurium and M. smegmatisis NAT. Structures of S. typhimurium (red) and M. smegmatis (green) NAT are superimposed on the basis of their first two domains. The conformational difference corresponds approximately to a rotation of the third domains around an axis as indicated by the arrow. Domains 1 (helical bundle), 2 (b-barrel), and 3 (mixed a/b) are labelled D1-D3.
Figure 6.
Figure 6. Geometry of the catalytic site of M. smegmatis NAT. Residues of the catalytic triad are shown, with hydrogen bonding distances indicated. Supportive electron density comes from the REFMAC weighted 2F[o] -F[c] electron density map, contoured at 0.25 e^ - Å -3. The labelled water molecule identifies the likely site of oxyanion binding.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2002, 318, 1071-1083) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
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.  
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.  
19018723 L.A.Stanley, and E.Sim (2008).
Update on the pharmacogenetics of NATs: structural considerations.
  Pharmacogenomics, 9, 1673-1693.  
18518853 S.Boukouvala, I.M.Westwood, N.J.Butcher, and G.Fakis (2008).
Current trends in N-acetyltransferase research arising from the 2007 International NAT Workshop.
  Pharmacogenomics, 9, 765-771.  
  17909290 B.Pluvinage, I.L.de 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.  
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.  
17635188 S.L.Kendall, M.Withers, C.N.Soffair, N.J.Moreland, S.Gurcha, B.Sidders, R.Frita, A.Ten Bokum, G.S.Besra, J.S.Lott, and N.G.Stoker (2007).
A highly conserved transcriptional repressor controls a large regulon involved in lipid degradation in Mycobacterium smegmatis and Mycobacterium tuberculosis.
  Mol Microbiol, 65, 684-699.  
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.  
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.  
15722451 J.Sandy, S.Holton, E.Fullam, E.Sim, and M.Noble (2005).
Binding of the anti-tubercular drug isoniazid to the arylamine N-acetyltransferase protein from Mycobacterium smegmatis.
  Protein Sci, 14, 775-782.
PDB code: 1w6f
  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.  
15117974 S.Bhakta, G.S.Besra, A.M.Upton, T.Parish, C.Sholto-Douglas-Vernon, K.J.Gibson, S.Knutton, S.Gordon, R.P.DaSilva, M.C.Anderton, and E.Sim (2004).
Arylamine N-acetyltransferase is required for synthesis of mycolic acids and complex lipids in Mycobacterium bovis BCG and represents a novel drug target.
  J Exp Med, 199, 1191-1199.  
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.  
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 code is shown on the right.