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PDBsum entry 1m4d
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protein ligands Protein-protein interface(s) links
Transferase PDB id
1m4d

 

 

 

 

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Contents
Protein chains
181 a.a. *
Ligands
TOY ×2
COA ×2
PAP
Waters ×236
* Residue conservation analysis
PDB id:
1m4d
Name: Transferase
Title: Aminoglycoside 2'-n-acetyltransferase from mycobacterium tuberculosis- complex with coenzyme a and tobramycin
Structure: Aminoglycoside 2'-n-acetyltransferase. Chain: a, b. Synonym: aminosugar n-acetyltransferase, aac(2')-ic. Engineered: yes
Source: Mycobacterium tuberculosis. Organism_taxid: 83332. Strain: h37rv. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
1.80Å     R-factor:   0.174     R-free:   0.211
Authors: M.W.Vetting,S.S.Hegde,F.Javid-Majd,J.S.Blanchard,S.L.Roderick
Key ref:
M.W.Vetting et al. (2002). Aminoglycoside 2'-N-acetyltransferase from Mycobacterium tuberculosis in complex with coenzyme A and aminoglycoside substrates. Nat Struct Biol, 9, 653-658. PubMed id: 12161746 DOI: 10.1038/nsb830
Date:
02-Jul-02     Release date:   28-Aug-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P9WQG9  (AAC2_MYCTU) -  Aminoglycoside 2'-N-acetyltransferase from Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Seq:
Struc: 		181 a.a.
181 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.3.1.-  - ?????
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

 

 
DOI no: 10.1038/nsb830 Nat Struct Biol 9:653-658 (2002)
PubMed id: 12161746  
 
 
Aminoglycoside 2'-N-acetyltransferase from Mycobacterium tuberculosis in complex with coenzyme A and aminoglycoside substrates.
M.W.Vetting, S.S.Hegde, F.Javid-Majd, J.S.Blanchard, S.L.Roderick.
 
  ABSTRACT  
 
AAC(2')-Ic catalyzes the coenzyme A (CoA)-dependent acetylation of the 2' hydroxyl or amino group of a broad spectrum of aminoglycosides. The crystal structure of the AAC(2')-Ic from Mycobacterium tuberculosis has been determined in the apo enzyme form and in ternary complexes with CoA and either tobramycin, kanamycin A or ribostamycin, representing the first structures of an aminoglycoside acetyltransferase bound to a drug. The overall fold of AAC(2')-Ic places it in the GCN5-related N-acetyltransferase (GNAT) superfamily. Although the physiological function of AAC(2')-Ic is uncertain, a structural analysis of these high-affinity aminoglycoside complexes suggests that the enzyme may acetylate a key biosynthetic intermediate of mycothiol, the major reducing agent in mycobacteria, and participate in the regulation of cellular redox potential.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. Comparison of bound aminoglycosides and the chemical mechanism of acyltransfer by AAC(2')-Ic. a, Stereo view of the superposition of tobramycin (blue), kanamycin A (green), and ribostamycin (red) in the aminoglycoside -AAC(2')-Ic complexes. The five water molecules that are conserved in all three ternary complexes are shown as red spheres. Protein coordinates are from AAC(2')-Ic in complex with ribostamycin and CoA. b, Chemical reaction mechanism of AAC(2')-Ic based on the AAC(2')-Ic ternary complexes. 		Figure 4.
Figure 4. Potential physiological function of AAC(2')-Ic. a, Proposed step in mycothiol biosynthesis that may be catalyzed by AAC(2')-Ic. b, Model of GlcN-Ins bound to AAC(2')-Ic. The differentiating hydroxyls of inositol compared with 2-deoxystreptamine are green, and their potential interactions with AAC(2')-Ic are red.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2002, 9, 653-658) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21286630 G.D.Wright (2011).
Molecular mechanisms of antibiotic resistance.
  Chem Commun (Camb), 47, 4055-4061.  
20397253 J.L.Houghton, K.D.Green, W.Chen, and S.Garneau-Tsodikova (2010).
The future of aminoglycosides: the end or renaissance?
  Chembiochem, 11, 880-902.  
19889644 K.Oda, Y.Matoba, M.Noda, T.Kumagai, and M.Sugiyama (2010).
Catalytic mechanism of bleomycin N-acetyltransferase proposed on the basis of its crystal structure.
  J Biol Chem, 285, 1446-1456.
PDB codes: 2zw4 2zw5 2zw6 2zw7
20822442 M.Morar, and G.D.Wright (2010).
The genomic enzymology of antibiotic resistance.
  Annu Rev Genet, 44, 25-51.  
20833577 M.S.Ramirez, and M.E.Tolmasky (2010).
Aminoglycoside modifying enzymes.
  Drug Resist Updat, 13, 151-171.  
20406434 T.M.Bakheet, and A.J.Doig (2010).
Properties and identification of antibiotic drug targets.
  BMC Bioinformatics, 11, 195.  
19448740 M.Demendi, and C.Creuzenet (2009).
Cj1123c (PglD), a multifaceted acetyltransferase from Campylobacter jejuni.
  Biochem Cell Biol, 87, 469-483.  
19856962 S.Shahzad-ul-Hussan, M.Cai, and C.A.Bewley (2009).
Unprecedented glycosidase activity at a lectin carbohydrate-binding site exemplified by the cyanobacterial lectin MVL.
  J Am Chem Soc, 131, 16500-16508.  
  18997321 M.W.Vetting, J.C.Errey, and J.S.Blanchard (2008).
Rv0802c from Mycobacterium tuberculosis: the first structure of a succinyltransferase with the GNAT fold.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 978-985.
PDB codes: 2vzy 2vzz
18774127 O.J.Barrett, A.Pushechnikov, M.Wu, and M.D.Disney (2008).
Studying aminoglycoside modification by the acetyltransferase class of resistance-causing enzymes via microarray.
  Carbohydr Res, 343, 2924-2931.  
18373682 T.Kotani, and H.Takagi (2008).
Identification of amino acid residues essential for the yeast N-acetyltransferase Mpr1 activity by site-directed mutagenesis.
  FEMS Yeast Res, 8, 607-614.  
19030604 V.K.Jothivasan, and C.J.Hamilton (2008).
Mycothiol: synthesis, biosynthesis and biological functions of the major low molecular weight thiol in actinomycetes.
  Nat Prod Rep, 25, 1091-1117.  
  17671368 D.Iino, Y.Takakura, M.Kuroiwa, R.Kawakami, Y.Sasaki, T.Hoshino, K.Ohsawa, A.Nakamura, and S.Yajima (2007).
Crystallization and preliminary crystallographic analysis of hygromycin B phosphotransferase from Escherichia coli.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 685-688.  
17516632 S.S.Hegde, J.Chandler, M.W.Vetting, M.Yu, and J.S.Blanchard (2007).
Mechanistic and structural analysis of human spermidine/spermine N1-acetyltransferase.
  Biochemistry, 46, 7187-7195.
PDB code: 2jev
16855251 M.N.Hung, E.Rangarajan, C.Munger, G.Nadeau, T.Sulea, and A.Matte (2006).
Crystal structure of TDP-fucosamine acetyltransferase (WecD) from Escherichia coli, an enzyme required for enterobacterial common antigen synthesis.
  J Bacteriol, 188, 5606-5617.
PDB codes: 2fs5 2ft0
17128971 R.C.Tyler, E.Bitto, C.E.Berndsen, C.A.Bingman, S.Singh, M.S.Lee, G.E.Wesenberg, J.M.Denu, G.N.Phillips, and J.L.Markley (2006).
Structure of Arabidopsis thaliana At1g77540 protein, a minimal acetyltransferase from the COG2388 family.
  Biochemistry, 45, 14325-14336.
PDB codes: 1xmt 2evn 2gdb 2il4
15798968 D.B.Werz, and P.H.Seeberger (2005).
Carbohydrates as the next frontier in pharmaceutical research.
  Chemistry, 11, 3194-3206.  
15695811 G.L.Card, N.A.Peterson, C.A.Smith, B.Rupp, B.M.Schick, and E.N.Baker (2005).
The crystal structure of Rv1347c, a putative antibiotic resistance protein from Mycobacterium tuberculosis, reveals a GCN5-related fold and suggests an alternative function in siderophore biosynthesis.
  J Biol Chem, 280, 13978-13986.
PDB code: 1yk3
15982889 J.P.Murry, and E.J.Rubin (2005).
New genetic approaches shed light on TB virulence.
  Trends Microbiol, 13, 366-372.  
16322579 T.A.Binkowski, A.Joachimiak, and J.Liang (2005).
Protein surface analysis for function annotation in high-throughput structural genomics pipeline.
  Protein Sci, 14, 2972-2981.  
15457538 D.M.Ratner, E.W.Adams, M.D.Disney, and P.H.Seeberger (2004).
Tools for glycomics: mapping interactions of carbohydrates in biological systems.
  Chembiochem, 5, 1375-1383.  
15123251 M.W.Vetting, S.Magnet, E.Nieves, S.L.Roderick, and J.S.Blanchard (2004).
A bacterial acetyltransferase capable of regioselective N-acetylation of antibiotics and histones.
  Chem Biol, 11, 565-573.
PDB codes: 1s3z 1s5k 1s60
12566434 D.D.Boehr, S.I.Jenkins, and G.D.Wright (2003).
The molecular basis of the expansive substrate specificity of the antibiotic resistance enzyme aminoglycoside acetyltransferase-6'-aminoglycoside phosphotransferase-2". The role of ASP-99 as an active site base important for acetyl transfer.
  J Biol Chem, 278, 12873-12880.  
12592013 D.L.Burk, N.Ghuman, L.E.Wybenga-Groot, and A.M.Berghuis (2003).
X-ray structure of the AAC(6')-Ii antibiotic resistance enzyme at 1.8 A resolution; examination of oligomeric arrangements in GNAT superfamily members.
  Protein Sci, 12, 426-437.
PDB code: 1n71
12936992 K.J.Dery, B.Søballe, M.S.Witherspoon, D.Bui, R.Koch, D.J.Sherratt, and M.E.Tolmasky (2003).
The aminoglycoside 6'-N-acetyltransferase type Ib encoded by Tn1331 is evenly distributed within the cell's cytoplasm.
  Antimicrob Agents Chemother, 47, 2897-2902.  
12930994 M.W.Vetting, S.L.Roderick, M.Yu, and J.S.Blanchard (2003).
Crystal structure of mycothiol synthase (Rv0819) from Mycobacterium tuberculosis shows structural homology to the GNAT family of N-acetyltransferases.
  Protein Sci, 12, 1954-1959.
PDB codes: 1ozp 1p0h
12925992 Q.Vicens, and E.Westhof (2003).
Molecular recognition of aminoglycoside antibiotics by ribosomal RNA and resistance enzymes: an analysis of x-ray crystal structures.
  Biopolymers, 70, 42-57.  
12679335 S.S.Hegde, and J.S.Blanchard (2003).
Kinetic and mechanistic characterization of recombinant Lactobacillus viridescens FemX (UDP-N-acetylmuramoyl pentapeptide-lysine N6-alanyltransferase).
  J Biol Chem, 278, 22861-22867.  
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.

 

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