PDBsum entry 2q3c

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protein ligands links
Transferase PDB id
Protein chain
300 a.a. *
Waters ×163
* Residue conservation analysis
PDB id:
Name: Transferase
Title: 2.1 a resolution crystal structure of o-acetylserine sulfhyd (oass) holoenzyme from mycobacterium tuberculosis in comple inhibitory peptide dfsi
Structure: Cysteine synthase a. Chain: a. Synonym: o-acetylserine sulfhydrylase a, o-acetylserine thi a, csase a. Engineered: yes. Dfsi inhibitory peptide. Chain: b. Engineered: yes
Source: Mycobacterium tuberculosis. Organism_taxid: 1773. Strain: rv2334. Gene: cysk. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Organism_taxid: 1773
2.10Å     R-factor:   0.188     R-free:   0.207
Authors: G.Schneider,R.Schnell
Key ref:
R.Schnell et al. (2007). Structural insights into catalysis and inhibition of O-acetylserine sulfhydrylase from Mycobacterium tuberculosis. Crystal structures of the enzyme alpha-aminoacrylate intermediate and an enzyme-inhibitor complex. J Biol Chem, 282, 23473-23481. PubMed id: 17567578 DOI: 10.1074/jbc.M703518200
30-May-07     Release date:   12-Jun-07    
Go to PROCHECK summary

Protein chain
P9WP55  (CYSK_MYCTU) -  O-acetylserine sulfhydrylase
310 a.a.
300 a.a.*
Key:    Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.  - Cysteine synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: O-acetyl-L-serine + hydrogen sulfide = L-cysteine + acetate
Bound ligand (Het Group name = SER)
matches with 60.00% similarity
+ hydrogen sulfide
Bound ligand (Het Group name = ILE)
matches with 60.00% similarity
Bound ligand (Het Group name = ASP)
matches with 50.00% similarity
      Cofactor: Pyridoxal 5'-phosphate
Pyridoxal 5'-phosphate
Bound ligand (Het Group name = PHE) matches with 42.00% similarity
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   1 term 
  Biological process     cellular amino acid biosynthetic process   3 terms 
  Biochemical function     transferase activity     2 terms  


DOI no: 10.1074/jbc.M703518200 J Biol Chem 282:23473-23481 (2007)
PubMed id: 17567578  
Structural insights into catalysis and inhibition of O-acetylserine sulfhydrylase from Mycobacterium tuberculosis. Crystal structures of the enzyme alpha-aminoacrylate intermediate and an enzyme-inhibitor complex.
R.Schnell, W.Oehlmann, M.Singh, G.Schneider.
Cysteine biosynthetic genes are up-regulated in the persistent phase of Mycobacterium tuberculosis, and the corresponding enzymes are therefore of interest as potential targets for novel antibacterial agents. cysK1 is one of these genes and has been annotated as coding for an O-acetylserine sulfhydrylase. Recombinant CysK1 is a pyridoxal phosphate (PLP)-dependent enzyme that catalyzes the conversion of O-acetylserine to cysteine. The crystal structure of the enzyme was determined to 1.8A resolution. CysK1 belongs to the family of fold type II PLP enzymes and is similar in structure to other O-acetylserine sulfhydrylases. We were able to trap the alpha-aminoacrylate reaction intermediate and determine its structure by cryocrystallography. Formation of the aminoacrylate complex is accompanied by a domain rotation resulting in active site closure. The aminoacrylate moiety is bound in the active site via the covalent linkage to the PLP cofactor and by hydrogen bonds of its carboxyl group to several enzyme residues. The catalytic lysine residue is positioned such that it can protonate the Calpha-carbon atom of the aminoacrylate only from the si-face, resulting in the formation of L-cysteine. CysK1 is competitively inhibited by a four-residue peptide derived from the C-terminal of serine acetyl transferase. The crystallographic analysis reveals that the peptide binds to the enzyme active site, suggesting that CysK1 forms an bi-enzyme complex with serine acetyl transferase, in a similar manner to other bacterial and plant O-acetylserine sulfhydrylases. The structure of the enzyme-peptide complex provides a framework for the design of strong binding inhibitors.
  Selected figure(s)  
Figure 3.
FIGURE 3. Structure of the complex of CysK1 with -aminoacrylate. A, superposition of holo-CysK1 (blue) and the CysK1-aminoacrylate complex (red) illustrating the conformational changes of the N-terminal domain leading to the closure of the active site. The covalent intermediate forming the external Schiff base with PLP is shown as a stick model (yellow). B, part of the 2F[o] - F[o] electron density map, contoured at 1.2 , showing formation of the -aminoacrylate intermediate. C, schematic showing the interactions of the reaction intermediate with enzyme residues in the active site. Hydrogen bonds are indicated by dashed lines. D, stereo view of the active site of the CysK1- -aminoacrylate intermediate complex. The red spheres indicate the positions of bound water molecules.
Figure 6.
FIGURE 6. Structure of the CysK1-peptide complex. A, stereo view of the active site of CysK1 with the bound DFSI peptide, shown in green. CysK1 amino acid residues are shown in yellow, and water molecules are shown as red spheres. B, part of the 2F[o] - F[o] electron density map at the peptide binding site in CysK1, contoured at 1.4 .
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2007, 282, 23473-23481) copyright 2007.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20033172 C.Zheng, L.Nie, L.Qian, Z.Wang, G.Liu, and J.Liu (2010).
K30, H150, and H168 are essential residues for coordinating pyridoxal 5'-phosphate of O-acetylserine sulfhydrylase from Acidithiobacillus ferrooxidans.
  Curr Microbiol, 60, 461-465.  
19928859 E.Salsi, A.S.Bayden, F.Spyrakis, A.Amadasi, B.Campanini, S.Bettati, T.Dodatko, P.Cozzini, G.E.Kellogg, P.F.Cook, S.L.Roderick, and A.Mozzarelli (2010).
Design of O-acetylserine sulfhydrylase inhibitors by mimicking nature.
  J Med Chem, 53, 345-356.
PDB codes: 3iqg 3iqh 3iqi
21081698 M.Koutmos, O.Kabil, J.L.Smith, and R.Banerjee (2010).
Structural basis for substrate activation and regulation by cystathionine beta-synthase (CBS) domains in cystathionine {beta}-synthase.
  Proc Natl Acad Sci U S A, 107, 20958-20963.
PDB codes: 3pc2 3pc3 3pc4
19213732 S.Kumaran, H.Yi, H.B.Krishnan, and J.M.Jez (2009).
Assembly of the cysteine synthase complex and the regulatory role of protein-protein interactions.
  J Biol Chem, 284, 10268-10275.  
18641144 C.Paige, S.D.Reid, P.C.Hanna, and A.Claiborne (2008).
The type III pantothenate kinase encoded by coaX is essential for growth of Bacillus anthracis.
  J Bacteriol, 190, 6271-6275.  
18350570 K.Chinthalapudi, M.Kumar, S.Kumar, S.Jain, N.Alam, and S.Gourinath (2008).
Crystal structure of native O-acetyl-serine sulfhydrylase from Entamoeba histolytica and its complex with cysteine: structural evidence for cysteine binding and lack of interactions with serine acetyl transferase.
  Proteins, 72, 1222-1232.
PDB codes: 2pqm 3bm5
18491919 P.Smith, P.H.Szu, C.Bui, H.W.Liu, and S.C.Tsai (2008).
Structure and mutagenic conversion of E1 dehydrase: at the crossroads of dehydration, amino transfer, and epimerization.
  Biochemistry, 47, 6329-6341.  
17894825 G.Zocher, U.Wiesand, and G.E.Schulz (2007).
High resolution structure and catalysis of O-acetylserine sulfhydrylase isozyme B from Escherichia coli.
  FEBS J, 274, 5382-5389.
PDB code: 2v03
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.