spacer
spacer

PDBsum entry 1qhx

Go to PDB code: 
protein ligands metals links
Transferase PDB id
1qhx
Jmol
Contents
Protein chain
178 a.a. *
Ligands
ATP
Metals
_MG
Waters ×100
* Residue conservation analysis
PDB id:
1qhx
Name: Transferase
Title: Chloramphenicol phosphotransferase in complex with atp from streptomyces venezuelae
Structure: Protein (chloramphenicol phosphotransferase). Chain: a. Synonym: cpt. Ec: 2.7.1.-
Source: Streptomyces venezuelae. Organism_taxid: 54571. Strain: isp5230
Biol. unit: Tetramer (from PDB file)
Resolution:
2.50Å     R-factor:   0.228     R-free:   0.238
Authors: T.Izard
Key ref: T.Izard and J.Ellis (2000). The crystal structures of chloramphenicol phosphotransferase reveal a novel inactivation mechanism. EMBO J, 19, 2690-2700. PubMed id: 10835366
Date:
31-May-99     Release date:   01-Jun-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q56148  (CPT_STRVP) -  Chloramphenicol 3-O phosphotransferase
Seq:
Struc:
178 a.a.
178 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     response to antibiotic   2 terms 
  Biochemical function     nucleotide binding     4 terms  

 

 
EMBO J 19:2690-2700 (2000)
PubMed id: 10835366  
 
 
The crystal structures of chloramphenicol phosphotransferase reveal a novel inactivation mechanism.
T.Izard, J.Ellis.
 
  ABSTRACT  
 
Chloramphenicol (Cm), produced by the soil bacterium Streptomyces venezuelae, is an inhibitor of bacterial ribosomal peptidyltransferase activity. The Cm-producing streptomycete modifies the primary (C-3) hydroxyl of the antibiotic by a novel Cm-inactivating enzyme, chloramphenicol 3-O-phosphotransferase (CPT). Here we describe the crystal structures of CPT in the absence and presence of bound substrates. The enzyme is dimeric in a sulfate-free solution and tetramerization is induced by ammonium sulfate, the crystallization precipitant. The tetrameric quaternary structure exhibits crystallographic 222 symmetry and has ATP binding pockets located at a crystallographic 2-fold axis. Steric hindrance allows only one ATP to bind per dimer within the tetramer. In addition to active site binding by Cm, an electron-dense feature resembling the enzyme's product is found at the other subunit interface. The structures of CPT suggest that an aspartate acts as a general base to accept a proton from the 3-hydroxyl of Cm, concurrent with nucleophilic attack of the resulting oxyanion on the gamma-phosphate of ATP. Comparison between liganded and substrate-free CPT structures highlights side chain movements of the active site's Arg136 guanidinium group of >9 A upon substrate binding.
 

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.  
20231391 T.Shakya, and G.D.Wright (2010).
Nucleotide selectivity of antibiotic kinases.
  Antimicrob Agents Chemother, 54, 1909-1913.  
19805283 Y.Araiso, R.L.Sherrer, R.Ishitani, J.M.Ho, D.Söll, and O.Nureki (2009).
Structure of a tRNA-dependent kinase essential for selenocysteine decoding.
  Proc Natl Acad Sci U S A, 106, 16215-16220.
PDB codes: 3a4l 3a4m 3a4n
18258747 H.Sugawara, N.Ueda, M.Kojima, N.Makita, T.Yamaya, and H.Sakakibara (2008).
Structural insight into the reaction mechanism and evolution of cytokinin biosynthesis.
  Proc Natl Acad Sci U S A, 105, 2734-2739.
PDB codes: 2ze5 2ze6 2ze7 2ze8
18174226 R.L.Sherrer, P.O'Donoghue, and D.Söll (2008).
Characterization and evolutionary history of an archaeal kinase involved in selenocysteinyl-tRNA formation.
  Nucleic Acids Res, 36, 1247-1259.  
  18540055 U.Kapp, S.Macedo, D.R.Hall, I.Leiros, S.M.McSweeney, and E.Mitchell (2008).
Structure of Deinococcus radiodurans tunicamycin-resistance protein (TmrD), a phosphotransferase.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 479-486.
PDB code: 2vli
17698003 J.A.Khan, S.Xiang, and L.Tong (2007).
Crystal structure of human nicotinamide riboside kinase.
  Structure, 15, 1005-1013.
PDB codes: 2qg6 2ql6
18277000 M.Hashimoto, T.Taguchi, S.Nishida, K.Ueno, K.Koizumi, M.Aburada, and K.Ichinose (2007).
Isolation of 8'-phosphate ester derivatives of amicoumacins: structure-activity relationship of hydroxy amino acid moiety.
  J Antibiot (Tokyo), 60, 752-756.  
17488720 S.K.Khoo, B.Loll, W.T.Chan, R.L.Shoeman, L.Ngoo, C.C.Yeo, and A.Meinhart (2007).
Molecular and structural characterization of the PezAT chromosomal toxin-antitoxin system of the human pathogen Streptococcus pneumoniae.
  J Biol Chem, 282, 19606-19618.
PDB code: 2p5t
16180279 A.Yonath (2005).
Antibiotics targeting ribosomes: resistance, selectivity, synergism and cellular regulation.
  Annu Rev Biochem, 74, 649-679.  
15940457 V.S.Hung, Y.Hatada, S.Goda, J.Lu, Y.Hidaka, Z.Li, M.Akita, Y.Ohta, K.Watanabe, H.Matsui, S.Ito, and K.Horikoshi (2005).
alpha-Glucosidase from a strain of deep-sea Geobacillus: a potential enzyme for the biosynthesis of complex carbohydrates.
  Appl Microbiol Biotechnol, 68, 757-765.  
15487937 A.Yonath, and A.Bashan (2004).
Ribosomal crystallography: initiation, peptide bond formation, and amino acid polymerization are hampered by antibiotics.
  Annu Rev Microbiol, 58, 233-251.  
15331605 D.Pettigrew, K.L.Anderson, J.Billington, E.Cota, P.Simpson, P.Urvil, F.Rabuzin, P.Roversi, B.Nowicki, L.du Merle, C.Le Bouguénec, S.Matthews, and S.M.Lea (2004).
High resolution studies of the Afa/Dr adhesin DraE and its interaction with chloramphenicol.
  J Biol Chem, 279, 46851-46857.
PDB codes: 1usq 1usz 1ut1 1ut2
15272163 K.N.Rao, C.G.Suresh, U.V.Katre, S.M.Gaikwad, and M.I.Khan (2004).
Two orthorhombic crystal structures of a galactose-specific lectin from Artocarpus hirsuta in complex with methyl-alpha-D-galactose.
  Acta Crystallogr D Biol Crystallogr, 60, 1404-1412.
PDB codes: 1toq 1tp8
15229886 N.Fernandez-Fuentes, A.Hermoso, J.Espadaler, E.Querol, F.X.Aviles, and B.Oliva (2004).
Classification of common functional loops of kinase super-families.
  Proteins, 56, 539-555.  
15130468 N.N.Suzuki, K.Koizumi, M.Fukushima, A.Matsuda, and F.Inagaki (2004).
Structural basis for the specificity, catalysis, and regulation of human uridine-cytidine kinase.
  Structure, 12, 751-764.
PDB codes: 1udw 1uei 1uej 1ufq 1uj2
15539072 S.Schwarz, C.Kehrenberg, B.Doublet, and A.Cloeckaert (2004).
Molecular basis of bacterial resistance to chloramphenicol and florfenicol.
  FEMS Microbiol Rev, 28, 519-542.  
15491801 T.Auerbach, A.Bashan, and A.Yonath (2004).
Ribosomal antibiotics: structural basis for resistance, synergism and selectivity.
  Trends Biotechnol, 22, 570-576.  
12538896 N.O'Toole, J.A.Barbosa, Y.Li, L.W.Hung, A.Matte, and M.Cygler (2003).
Crystal structure of a trimeric form of dephosphocoenzyme A kinase from Escherichia coli.
  Protein Sci, 12, 327-336.
PDB code: 1n3b
12837781 T.Izard (2003).
A novel adenylate binding site confers phosphopantetheine adenylyltransferase interactions with coenzyme A.
  J Bacteriol, 185, 4074-4080.
PDB code: 1h1t
11796714 A.Galinier, J.P.Lavergne, C.Geourjon, S.Fieulaine, S.Nessler, and J.M.Jault (2002).
A new family of phosphotransferases with a P-loop motif.
  J Biol Chem, 277, 11362-11367.  
11909870 R.A.Maxwell, W.H.Welch, F.M.Horodyski, K.M.Schegg, and D.A.Schooley (2002).
Juvenile hormone diol kinase. II. Sequencing, cloning, and molecular modeling of juvenile hormone-selective diol kinase from Manduca sexta.
  J Biol Chem, 277, 21882-21890.  
11468347 T.Izard (2001).
Structural basis for chloramphenicol tolerance in Streptomyces venezuelae by chloramphenicol phosphotransferase activity.
  Protein Sci, 10, 1508-1513.
PDB codes: 1grq 1grr
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.