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Lyase PDB id
2gqn
Jmol
Contents
Protein chains
391 a.a. *
Ligands
BLP ×2
Waters ×947
* Residue conservation analysis
PDB id:
2gqn
Name: Lyase
Title: Cystathionine beta-lyase (cbl) from escherichia coli in comp n-hydrazinocarbonylmethyl-2-nitro-benzamide
Structure: Cystathionine beta-lyase. Chain: a, b. Synonym: cbl, beta-cystathionase, cysteine lyase. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Gene: metc. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
1.80Å     R-factor:   0.177     R-free:   0.227
Authors: R.Summerfield,M.S.Junop
Key ref: L.J.Ejim et al. (2007). Inhibitors of bacterial cystathionine beta-lyase: leads for new antimicrobial agents and probes of enzyme structure and function. J Med Chem, 50, 755-764. PubMed id: 17300162 DOI: 10.1021/jm061132r
Date:
21-Apr-06     Release date:   06-Mar-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P06721  (METC_ECOLI) -  Cystathionine beta-lyase metC
Seq:
Struc: 		395 a.a.
391 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.4.4.1.8  - Cystathionine beta-lyase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: L-cystathionine + H2O = L-homocysteine + NH3 + pyruvate
L-cystathionine
 + H(2)O
 = L-homocysteine
 + NH(3)
 + pyruvate
      Cofactor: Pyridoxal 5'-phosphate
Pyridoxal 5'-phosphate
Bound ligand (Het Group name = BLP) matches with 45.45% similarity
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     cellular amino acid metabolic process   3 terms 
  Biochemical function     catalytic activity     5 terms  

 

 
    reference    
 
 
DOI no: 10.1021/jm061132r J Med Chem 50:755-764 (2007)
PubMed id: 17300162  
 
 
Inhibitors of bacterial cystathionine beta-lyase: leads for new antimicrobial agents and probes of enzyme structure and function.
L.J.Ejim, J.E.Blanchard, K.P.Koteva, R.Sumerfield, N.H.Elowe, J.D.Chechetto, E.D.Brown, M.S.Junop, G.D.Wright.
 
  ABSTRACT  
 
The biosynthesis of methionine is an attractive antibiotic target given its importance in protein and DNA metabolism and its absence in mammals. We have performed a high-throughput screen of the methionine biosynthesis enzyme cystathionine beta-lyase (CBL) against a library of 50 000 small molecules and have identified several compounds that inhibit CBL enzyme activity in vitro. These hit molecules were of two classes: those that blocked CBL activity with mixed steady-state inhibition and those that covalently interacted with the enzyme at the active site pyridoxal phosphate cofactor with slow-binding inhibition kinetics. We determined the crystal structure of one of the slow-binding inhibitors in complex with CBL and used this structure as a guide in the synthesis of a small, focused library of analogues, some of which had improved enzyme inhibition properties. These studies provide the first lead molecules for antimicrobial agents that target cystathionine beta-lyase in methionine biosynthesis.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
  20014435 P.H.Lodha, A.F.Jaworski, and S.M.Aitken (2010).
Characterization of site-directed mutants of residues R58, R59, D116, W340 and R372 in the active site of E. coli cystathionine beta-lyase.
  Protein Sci, 19, 383-391.  
19370061 A.Farsi, P.H.Lodha, J.E.Skanes, H.Los, N.Kalidindi, and S.M.Aitken (2009).
Interconversion of a pair of active-site residues in Escherichia coli cystathionine gamma-synthase, E. coli cystathionine beta-lyase, and Saccharomyces cerevisiae cystathionine gamma-lyase and development of tools for the investigation of their mechanisms and reaction specificity.
  Biochem Cell Biol, 87, 445-457.  
19448746 P.H.Lodha, H.Shadnia, C.M.Woodhouse, J.S.Wright, and S.M.Aitken (2009).
Investigation of residues Lys112, Glu136, His138, Gly247, Tyr248, and Asp249 in the active site of yeast cystathionine beta-synthase.
  Biochem Cell Biol, 87, 531-540.  
18519725 A.A.Miller, G.L.Bundy, J.E.Mott, J.E.Skepner, T.P.Boyle, D.W.Harris, A.E.Hromockyj, K.R.Marotti, G.E.Zurenko, J.B.Munzner, M.T.Sweeney, G.F.Bammert, J.C.Hamel, C.W.Ford, W.Z.Zhong, D.R.Graber, G.E.Martin, F.Han, L.A.Dolak, E.P.Seest, J.C.Ruble, G.M.Kamilar, J.R.Palmer, L.S.Banitt, A.R.Hurd, and M.R.Barbachyn (2008).
Discovery and characterization of QPT-1, the progenitor of a new class of bacterial topoisomerase inhibitors.
  Antimicrob Agents Chemother, 52, 2806-2812.  
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.