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Transferase PDB id
1kk5
Jmol
Contents
Protein chains
(+ 0 more) 206 a.a. *
Waters ×150
* Residue conservation analysis
PDB id:
1kk5
Name: Transferase
Title: Crystal structure of vat(d) (form ii)
Structure: Streptogramin a acetyltransferase. Chain: a, b, c, d, e, f. Engineered: yes
Source: Enterococcus faecium. Organism_taxid: 1352. Gene: sata. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Trimer (from PQS)
Resolution:
2.70Å     R-factor:   0.189     R-free:   0.256
Authors: M.Sugantino,S.L.Roderick
Key ref:
M.Sugantino and S.L.Roderick (2002). Crystal structure of Vat(D): an acetyltransferase that inactivates streptogramin group A antibiotics. Biochemistry, 41, 2209-2216. PubMed id: 11841212 DOI: 10.1021/bi011991b
Date:
06-Dec-01     Release date:   20-Feb-02    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
P50870  (VATD_ENTFC) -  Streptogramin A acetyltransferase
Seq:
Struc: 		209 a.a.
206 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     response to antibiotic   1 term 
  Biochemical function     transferase activity     2 terms  

 

 
DOI no: 10.1021/bi011991b Biochemistry 41:2209-2216 (2002)
PubMed id: 11841212  
 
 
Crystal structure of Vat(D): an acetyltransferase that inactivates streptogramin group A antibiotics.
M.Sugantino, S.L.Roderick.
 
  ABSTRACT  
 
The streptogramin class of antibiotics act to inhibit bacterial protein synthesis, and their semisynthetic derivatives, such as dalfopristin-quinupristin (Synercid), are used to treat serious or life-threatening infections due to multiply antibiotic resistant bacteria. Acquired resistance of the nosocomial pathogen Enterococcus faecium to the group A component of natural and semisynthetic streptogramin mixtures is a prerequisite for the streptogramin resistance phenotype and is mediated by a streptogramin acetyltransferase. The crystal structure of Vat(D), a streptogramin acetyltransferase from a human urinary isolate of E. faecium, has been determined as an apoenzyme and in complex with either acetyl-CoA or virginiamycin M1 and CoA. These structures illustrate the location and arrangement of residues at the active site, and point to His 82 as a residue that may function as a general base. The structural similarity of Vat(D) to the xenobiotic acetyltransferase from Pseudomonas aeruginosa indicates similarities in the catalytic mechanism for these enzymes as well as several shared and distinctive antibiotic binding interactions between these enzymes and their respective substrates. These results reveal the molecular basis for a reaction by which Gram-positive cocci acquire resistance to a last resort antibiotic.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20822442 M.Morar, and G.D.Wright (2010).
The genomic enzymology of antibiotic resistance.
  Annu Rev Genet, 44, 25-51.  
19448740 M.Demendi, and C.Creuzenet (2009).
Cj1123c (PglD), a multifaceted acetyltransferase from Campylobacter jejuni.
  Biochem Cell Biol, 87, 469-483.  
19364865 N.García, G.Gutiérrez, M.Lorenzo, S.Vadillo, S.Píriz, and A.Quesada (2009).
Gene Context and DNA rearrangements in the carbapenemase locus of division II strains of Bacteroides fragilis.
  Antimicrob Agents Chemother, 53, 2677-2678.  
18667421 N.B.Olivier, and B.Imperiali (2008).
Crystal Structure and Catalytic Mechanism of PglD from Campylobacter jejuni.
  J Biol Chem, 283, 27937-27946.
PDB codes: 3bss 3bsw 3bsy
17519228 A.K.Bergfeld, H.Claus, U.Vogel, and M.Mühlenhoff (2007).
Biochemical characterization of the polysialic acid-specific O-acetyltransferase NeuO of Escherichia coli K1.
  J Biol Chem, 282, 22217-22227.  
17277795 G.D.Wright (2007).
The antibiotic resistome: the nexus of chemical and genetic diversity.
  Nat Rev Microbiol, 5, 175-186.  
17563376 M.Korczynska, T.A.Mukhtar, G.D.Wright, and A.M.Berghuis (2007).
Structural basis for streptogramin B resistance in Staphylococcus aureus by virginiamycin B lyase.
  Proc Natl Acad Sci U S A, 104, 10388-10393.
PDB codes: 2z2n 2z2o 2z2p
16102001 C.Q.Wenzel, C.Daniels, R.A.Keates, D.Brewer, and J.S.Lam (2005).
Evidence that WbpD is an N-acetyltransferase belonging to the hexapeptide acyltransferase superfamily and an important protein for O-antigen biosynthesis in Pseudomonas aeruginosa PAO1.
  Mol Microbiol, 57, 1288-1303.  
15778971 D.G.Covell, A.Wallqvist, R.Huang, N.Thanki, A.A.Rabow, and X.J.Lu (2005).
Linking tumor cell cytotoxicity to mechanism of drug action: an integrated analysis of gene expression, small-molecule screening and structural databases.
  Proteins, 59, 403-433.  
15834559 J.Dang, R.P.Metzger, R.T.Brownlee, C.A.Ng, M.Bergdahl, and F.Separovic (2005).
The conformational flexibility of the antibiotic virginiamycin M(1).
  Eur Biophys J, 34, 383-388.  
15211513 L.L.Videau, W.B.Arendall, and J.S.Richardson (2004).
The cis-Pro touch-turn: a rare motif preferred at functional sites.
  Proteins, 56, 298-309.  
15390264 W.Qiu, R.Shi, M.L.Lu, M.Zhou, P.H.Roy, J.Lapointe, and S.X.Lin (2004).
Crystal structure of chloramphenicol acetyltransferase B2 encoded by the multiresistance transposon Tn2424.
  Proteins, 57, 858-861.  
12771141 L.E.Kehoe, J.Snidwongse, P.Courvalin, J.B.Rafferty, and I.A.Murray (2003).
Structural basis of Synercid (quinupristin-dalfopristin) resistance in Gram-positive bacterial pathogens.
  J Biol Chem, 278, 29963-29970.
PDB codes: 1mr7 1mr9 1mrl
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.