PDBsum entry 1oas

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Lyase PDB id
Protein chains
315 a.a. *
PLP ×2
Waters ×408
* Residue conservation analysis
PDB id:
Name: Lyase
Title: O-acetylserine sulfhydrylase from salmonella typhimurium
Structure: O-acetylserine sulfhydrylase. Chain: a, b. Synonym: cystein synthase. Engineered: yes
Source: Salmonella typhimurium. Organism_taxid: 602. Expressed in: salmonella typhimurium. Expression_system_taxid: 602
Biol. unit: Dimer (from PQS)
2.20Å     R-factor:   0.172     R-free:   0.200
Authors: P.Burkhard,G.S.J.Rao,E.Hohenester,K.D.Schnackerz,P.F.Cook, J.N.Jansonius
Key ref:
P.Burkhard et al. (1998). Three-dimensional structure of O-acetylserine sulfhydrylase from Salmonella typhimurium. J Mol Biol, 283, 121-133. PubMed id: 9761678 DOI: 10.1006/jmbi.1998.2037
29-Jan-99     Release date:   28-Jan-00    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P0A1E3  (CYSK_SALTY) -  Cysteine synthase A
323 a.a.
315 a.a.*
Key:    PfamA domain  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
+ hydrogen sulfide
= L-cysteine
+ acetate
      Cofactor: Pyridoxal 5'-phosphate
Pyridoxal 5'-phosphate
Bound ligand (Het Group name = PLP) matches with 93.75% similarity
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   4 terms 
  Biochemical function     catalytic activity     3 terms  


DOI no: 10.1006/jmbi.1998.2037 J Mol Biol 283:121-133 (1998)
PubMed id: 9761678  
Three-dimensional structure of O-acetylserine sulfhydrylase from Salmonella typhimurium.
P.Burkhard, G.S.Rao, E.Hohenester, K.D.Schnackerz, P.F.Cook, J.N.Jansonius.
The last step in cysteine biosynthesis in enteric bacteria is catalyzed by the pyridoxal 5'-phosphate-dependent enzyme O-acetylserine sulfhydrylase. Here we report the crystal structure at 2.2 A resolution of the A-isozyme of O-acetylserine sulfhydrylase isolated from Salmonella typhimurium. O-acetylserine sulfhydrylase shares the same fold with tryptophan synthase-beta from Salmonella typhimurium but the sequence identity level is below 20%. There are some major structural differences: the loops providing the interface to the alpha-subunit in tryptophan synthase-beta and two surface helices of tryptophan synthase-beta are missing in O-acetylserine sulfhydrylase. The hydrophobic channel for indole transport from the alpha to the beta active site of tryptophan synthase-beta is, not unexpectedly, also absent in O-acetylserine sulfhydrylase. The dimer interface, on the other hand, is more or less conserved in the two enzymes. The active site cleft of O-acetylserine sulfhydrylase is wider and therefore more exposed to the solvent. A possible binding site for the substrate O-acetylserine is discussed.
  Selected figure(s)  
Figure 2.
Figure 2. Schematic representation of the tertiary fold of a dimer of OASS-A. The central b-sheets are colored red and the surrounding a-helices are colored blue. In ball and stick representation are the active site Lys41 (yellow) and the cofactor PLP (green; the covalent link is not shown). The view is down the non-crystallographic 2-fold axis which relates the two subunits of the dimer. (Figure made using the program MOLSCRIPT; [Kraulis 1991]).
Figure 4.
Figure 4. The active-site residues of OASS-A with the cofactor PLP covalently bound in Schiff base linkage to Lys41. The phosphate group of the cofactor is bound at the N terminus of helix 7 (left, first turn shown in ball and stick representation), which interacts with the positive end of its dipole with the negative charge of the phosphate group. Each non-ester oxygen of the phosphate of PLP receives two hydrogen bonds from the phosphate binding portion of the protein (Gly176 to Thr180). Four of the H-bond donors are peptide NH groups. Helix 2 (right, first turn shown in ball and stick representation) generates also a positive dipole moment on the right-hand side of the cofactor and is proposed to interact with the carboxylate group of the substrate OAS (see Figure 5). The nitrogen N1 of PLP is hydrogen-bonded to Ser272. The cofactor PLP is shown superimposed on an "omit map" with only PLP left out of the structure factor calculation, contoured at 4s. (Figure made using the program O; [Jones et al 1991]).
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1998, 283, 121-133) copyright 1998.  
  Figures were selected by an automated process.  

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
19640845 M.Goto, T.Yamauchi, N.Kamiya, I.Miyahara, T.Yoshimura, H.Mihara, T.Kurihara, K.Hirotsu, and N.Esaki (2009).
Crystal structure of a homolog of mammalian serine racemase from Schizosaccharomyces pombe.
  J Biol Chem, 284, 25944-25952.
PDB codes: 1wtc 2zr8
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.  
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.  
18771296 C.T.Jurgenson, K.E.Burns, T.P.Begley, and S.E.Ealick (2008).
Crystal structure of a sulfur carrier protein complex found in the cysteine biosynthetic pathway of Mycobacterium tuberculosis.
  Biochemistry, 47, 10354-10364.
PDB codes: 3dwg 3dwi 3dwm
18799456 D.Agren, R.Schnell, W.Oehlmann, M.Singh, and G.Schneider (2008).
Cysteine Synthase (CysM) of Mycobacterium tuberculosis Is an O-Phosphoserine Sulfhydrylase: EVIDENCE FOR AN ALTERNATIVE CYSTEINE BIOSYNTHESIS PATHWAY IN MYCOBACTERIA.
  J Biol Chem, 283, 31567-31574.
PDB code: 3dki
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
  17554175 C.Krishna, R.Jain, T.Kashav, D.Wadhwa, N.Alam, and S.Gourinath (2007).
Crystallization and preliminary crystallographic analysis of cysteine synthase from Entamoeba histolytica.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 512-515.  
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
17567578 R.Schnell, W.Oehlmann, M.Singh, and G.Schneider (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.
PDB codes: 2q3b 2q3c 2q3d
16319072 C.Mas-Droux, V.Biou, and R.Dumas (2006).
Allosteric threonine synthase. Reorganization of the pyridoxal phosphate site upon asymmetric activation through S-adenosylmethionine binding to a novel site.
  J Biol Chem, 281, 5188-5196.
PDB codes: 2c2b 2c2g
17046821 D.K.Simanshu, H.S.Savithri, and M.R.Murthy (2006).
Crystal structures of Salmonella typhimurium biodegradative threonine deaminase and its complex with CMP provide structural insights into ligand-induced oligomerization and enzyme activation.
  J Biol Chem, 281, 39630-39641.
PDB codes: 2gn0 2gn1 2gn2
16735516 G.D.Westrop, G.Goodall, J.C.Mottram, and G.H.Coombs (2006).
Cysteine biosynthesis in Trichomonas vaginalis involves cysteine synthase utilizing O-phosphoserine.
  J Biol Chem, 281, 25062-25075.  
16386330 M.Wirtz, and R.Hell (2006).
Functional analysis of the cysteine synthase protein complex from plants: structural, biochemical and regulatory properties.
  J Plant Physiol, 163, 273-286.  
15987896 B.Campanini, F.Speroni, E.Salsi, P.F.Cook, S.L.Roderick, B.Huang, S.Bettati, and A.Mozzarelli (2005).
Interaction of serine acetyltransferase with O-acetylserine sulfhydrylase active site: evidence from fluorescence spectroscopy.
  Protein Sci, 14, 2115-2124.  
15838047 B.Huang, M.W.Vetting, and S.L.Roderick (2005).
The active site of O-acetylserine sulfhydrylase is the anchor point for bienzyme complex formation with serine acetyltransferase.
  J Bacteriol, 187, 3201-3205.
PDB code: 1y7l
16166087 E.R.Bonner, R.E.Cahoon, S.M.Knapke, and J.M.Jez (2005).
Molecular basis of cysteine biosynthesis in plants: structural and functional analysis of O-acetylserine sulfhydrylase from Arabidopsis thaliana.
  J Biol Chem, 280, 38803-38813.
PDB codes: 1z7w 1z7y
15890029 K.H.Jhee, and W.D.Kruger (2005).
The role of cystathionine beta-synthase in homocysteine metabolism.
  Antioxid Redox Signal, 7, 813-822.  
16307301 M.Wirtz, and M.Droux (2005).
Synthesis of the sulfur amino acids: cysteine and methionine.
  Photosynth Res, 86, 345-362.  
15073190 W.M.Rabeh, and P.F.Cook (2004).
Structure and mechanism of O-acetylserine sulfhydrylase.
  J Biol Chem, 279, 26803-26806.  
12813039 B.Campanini, S.Raboni, S.Vaccari, L.Zhang, P.F.Cook, T.L.Hazlett, A.Mozzarelli, and S.Bettati (2003).
Surface-exposed tryptophan residues are essential for O-acetylserine sulfhydrylase structure, function, and stability.
  J Biol Chem, 278, 37511-37519.  
12644499 K.Mino, and K.Ishikawa (2003).
Characterization of a novel thermostable O-acetylserine sulfhydrylase from Aeropyrum pernix K1.
  J Bacteriol, 185, 2277-2284.  
12554945 K.Mino, Y.Oda, M.Ataka, and K.Ishikawa (2003).
Crystallization and preliminary X-ray diffraction analysis of O-acetylserine sulfhydrylase from Aeropyrum pernix K1.
  Acta Crystallogr D Biol Crystallogr, 59, 338-340.  
12952961 R.Omi, M.Goto, I.Miyahara, H.Mizuguchi, H.Hayashi, H.Kagamiyama, and K.Hirotsu (2003).
Crystal structures of threonine synthase from Thermus thermophilus HB8: conformational change, substrate recognition, and mechanism.
  J Biol Chem, 278, 46035-46045.
PDB codes: 1uim 1uin 1uiq 1v7c
12882962 T.Ose, A.Fujino, M.Yao, N.Watanabe, M.Honma, and I.Tanaka (2003).
Reaction intermediate structures of 1-aminocyclopropane-1-carboxylate deaminase: insight into PLP-dependent cyclopropane ring-opening reaction.
  J Biol Chem, 278, 41069-41076.
PDB codes: 1j0c 1j0d 1j0e
12081500 J.Wei, Q.X.Tang, O.Varlamova, C.Roche, R.Lee, and T.S.Leyh (2002).
Cysteine biosynthetic enzymes are the pieces of a metabolic energy pump.
  Biochemistry, 41, 8493-8498.  
11756443 M.Garrido-Franco, S.Ehlert, A.Messerschmidt, S.Marinkovic', R.Huber, B.Laber, G.P.Bourenkov, and T.Clausen (2002).
Structure and function of threonine synthase from yeast.
  J Biol Chem, 277, 12396-12405.
PDB code: 1kl7
11948191 S.Taoka, and R.Banerjee (2002).
Stopped-flow kinetic analysis of the reaction catalyzed by the full-length yeast cystathionine beta-synthase.
  J Biol Chem, 277, 22421-22425.  
11259310 G.Chirico, S.Bettati, A.Mozzarelli, Y.Chen, J.D.Müller, and E.Gratton (2001).
Molecular heterogeneity of O-acetylserine sulfhydrylase by two-photon excited fluorescence fluctuation spectroscopy.
  Biophys J, 80, 1973-1985.  
11933244 K.Soda, T.Yoshimura, and N.Esaki (2001).
Stereospecificity for the hydrogen transfer of pyridoxal enzyme reactions.
  Chem Rec, 1, 373-384.  
11344332 K.Thomazeau, G.Curien, R.Dumas, and V.Biou (2001).
Crystal structure of threonine synthase from Arabidopsis thaliana.
  Protein Sci, 10, 638-648.
PDB code: 1e5x
11173483 M.Janosik, M.Meier, V.Kery, J.Oliveriusova, P.Burkhard, and J.P.Kraus (2001).
Crystallization and preliminary X-ray diffraction analysis of the active core of human recombinant cystathionine beta-synthase: an enzyme involved in vascular disease.
  Acta Crystallogr D Biol Crystallogr, 57, 289-291.  
11483494 M.Meier, M.Janosik, V.Kery, J.P.Kraus, and P.Burkhard (2001).
Structure of human cystathionine beta-synthase: a unique pyridoxal 5'-phosphate-dependent heme protein.
  EMBO J, 20, 3910-3916.
PDB code: 1jbq
11168407 M.Wirtz, O.Berkowitz, M.Droux, and R.Hell (2001).
The cysteine synthase complex from plants. Mitochondrial serine acetyltransferase from Arabidopsis thaliana carries a bifunctional domain for catalysis and protein-protein interaction.
  Eur J Biochem, 268, 686-693.  
11685243 P.Burkhard, P.Dominici, C.Borri-Voltattorni, J.N.Jansonius, and V.N.Malashkevich (2001).
Structural insight into Parkinson's disease treatment from drug-inhibited DOPA decarboxylase.
  Nat Struct Biol, 8, 963-967.
PDB codes: 1js3 1js6
10673430 G.Schneider, H.Käck, and Y.Lindqvist (2000).
The manifold of vitamin B6 dependent enzymes.
  Structure, 8, R1-R6.  
10956046 K.H.Jhee, P.McPhie, and E.W.Miles (2000).
Domain architecture of the heme-independent yeast cystathionine beta-synthase provides insights into mechanisms of catalysis and regulation.
  Biochemistry, 39, 10548-10556.  
10993149 K.Mino, T.Yamanoue, T.Sakiyama, N.Eisaki, A.Matsuyama, and K.Nakanishi (2000).
Effects of bienzyme complex formation of cysteine synthetase from escherichia coli on some properties and kinetics.
  Biosci Biotechnol Biochem, 64, 1628-1640.  
10429206 B.Laber, W.Maurer, C.Hanke, S.Gräfe, S.Ehlert, A.Messerschmidt, and T.Clausen (1999).
Characterization of recombinant Arabidopsis thaliana threonine synthase.
  Eur J Biochem, 263, 212-221.  
10593940 H.S.Ro, and E.W.Miles (1999).
Structure and function of the tryptophan synthase alpha(2)beta(2) complex. Roles of beta subunit histidine 86.
  J Biol Chem, 274, 36439-36445.  
10601247 K.D.Schnackerz, C.H.Tai, R.K.Pötsch, and P.F.Cook (1999).
Substitution of pyridoxal 5'-phosphate in D-serine dehydratase from Escherichia coli by cofactor analogues provides information on cofactor binding and catalysis.
  J Biol Chem, 274, 36935-36943.  
9914259 J.N.Jansonius (1998).
Structure, evolution and action of vitamin B6-dependent enzymes.
  Curr Opin Struct Biol, 8, 759-769.  
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.