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PDBsum entry 1cs1

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protein ligands Protein-protein interface(s) links
Lyase PDB id
1cs1
Jmol
Contents
Protein chains
384 a.a. *
Ligands
DHD
Waters ×1301
* Residue conservation analysis
PDB id:
1cs1
Name: Lyase
Title: Cystathionine gamma-synthase (cgs) from escherichia coli
Structure: Protein (cystathionine gamma-synthase). Chain: a, b, c, d. Synonym: cgs. Engineered: yes. Other_details: plp bound as cofactor to lys 198
Source: Escherichia coli. Organism_taxid: 562. Strain: dh5. Gene: metb. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Tetramer (from PQS)
Resolution:
1.50Å     R-factor:   0.200     R-free:   0.255
Authors: T.Clausen,A.Messerschmidt
Key ref: T.Clausen et al. (1998). Crystal structure of Escherichia coli cystathionine gamma-synthase at 1.5 A resolution. EMBO J, 17, 6827-6838. PubMed id: 9843488
Date:
23-Sep-98     Release date:   27-Sep-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P00935  (METB_ECOLI) -  Cystathionine gamma-synthase
Seq:
Struc:
386 a.a.
384 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.2.5.1.48  - Cystathionine gamma-synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: O4-succinyl-L-homoserine + L-cysteine = L-cystathionine + succinate
O(4)-succinyl-L-homoserine
+ L-cysteine
= L-cystathionine
+
succinate
Bound ligand (Het Group name = DHD)
matches with 58.00% similarity
      Cofactor: Pyridoxal 5'-phosphate
Pyridoxal 5'-phosphate
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 biosynthetic process   2 terms 
  Biochemical function     catalytic activity     4 terms  

 

 
    reference    
 
 
EMBO J 17:6827-6838 (1998)
PubMed id: 9843488  
 
 
Crystal structure of Escherichia coli cystathionine gamma-synthase at 1.5 A resolution.
T.Clausen, R.Huber, L.Prade, M.C.Wahl, A.Messerschmidt.
 
  ABSTRACT  
 
The transsulfuration enzyme cystathionine gamma-synthase (CGS) catalyses the pyridoxal 5'-phosphate (PLP)-dependent gamma-replacement of O-succinyl-L-homoserine and L-cysteine, yielding L-cystathionine. The crystal structure of the Escherichia coli enzyme has been solved by molecular replacement with the known structure of cystathionine beta-lyase (CBL), and refined at 1.5 A resolution to a crystallographic R-factor of 20.0%. The enzyme crystallizes as an alpha4 tetramer with the subunits related by non-crystallographic 222 symmetry. The spatial fold of the subunits, with three functionally distinct domains and their quaternary arrangement, is similar to that of CBL. Previously proposed reaction mechanisms for CGS can be checked against the structural model, allowing interpretation of the catalytic and substrate-binding functions of individual active site residues. Enzyme-substrate models pinpoint specific residues responsible for the substrate specificity, in agreement with structural comparisons with CBL. Both steric and electrostatic designs of the active site seem to achieve proper substrate selection and productive orientation. Amino acid sequence and structural alignments of CGS and CBL suggest that differences in the substrate-binding characteristics are responsible for the different reaction chemistries. Because CGS catalyses the only known PLP-dependent replacement reaction at Cgamma of certain amino acids, the results will help in our understanding of the chemical versatility of PLP.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20146062 A.S.El-Sayed (2010).
Microbial L-methioninase: production, molecular characterization, and therapeutic applications.
  Appl Microbiol Biotechnol, 86, 445-467.  
  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.  
19200371 P.Patel, M.Vatish, J.Heptinstall, R.Wang, and R.J.Carson (2009).
The endogenous production of hydrogen sulphide in intrauterine tissues.
  Reprod Biol Endocrinol, 7, 10.  
19019829 Q.Sun, R.Collins, S.Huang, L.Holmberg-Schiavone, G.S.Anand, C.H.Tan, S.van-den-Berg, L.W.Deng, P.K.Moore, T.Karlberg, and J.Sivaraman (2009).
Structural Basis for the Inhibition Mechanism of Human Cystathionine {gamma}-Lyase, an Enzyme Responsible for the Production of H2S.
  J Biol Chem, 284, 3076-3085.
PDB codes: 2nmp 3cog 3elp
18603802 D.Kudou, S.Misaki, M.Yamashita, T.Tamura, N.Esaki, and K.Inagaki (2008).
The role of cysteine 116 in the active site of the antitumor enzyme L-methionine gamma-lyase from Pseudomonas putida.
  Biosci Biotechnol Biochem, 72, 1722-1730.  
18093968 O.M.Ganichkin, X.M.Xu, B.A.Carlson, H.Mix, D.L.Hatfield, V.N.Gladyshev, and M.C.Wahl (2008).
Structure and catalytic mechanism of eukaryotic selenocysteine synthase.
  J Biol Chem, 283, 5849-5865.
PDB codes: 3bc8 3bca 3bcb
17225104 O.Cholet, A.Hénaut, and P.Bonnarme (2007).
Transcriptional analysis of L-methionine catabolism in Brevibacterium linens ATCC9175.
  Appl Microbiol Biotechnol, 74, 1320-1332.  
15281129 K.Manikandan, and S.Ramakumar (2004).
The occurrence of C--H...O hydrogen bonds in alpha-helices and helix termini in globular proteins.
  Proteins, 56, 768-781.  
12715888 A.Messerschmidt, M.Worbs, C.Steegborn, M.C.Wahl, R.Huber, B.Laber, and T.Clausen (2003).
Determinants of enzymatic specificity in the Cys-Met-metabolism PLP-dependent enzymes family: crystal structure of cystathionine gamma-lyase from yeast and intrafamiliar structure comparison.
  Biol Chem, 384, 373-386.
PDB code: 1n8p
12028377 R.A.Carter, P.S.Worsley, G.Sawers, G.L.Challis, M.J.Dilworth, K.C.Carson, J.A.Lawrence, M.Wexler, A.W.Johnston, and K.H.Yeoman (2002).
The vbs genes that direct synthesis of the siderophore vicibactin in Rhizobium leguminosarum: their expression in other genera requires ECF sigma factor RpoI.
  Mol Microbiol, 44, 1153-1166.  
11483578 L.A.Nahum, and M.Riley (2001).
Divergence of function in sequence-related groups of Escherichia coli proteins.
  Genome Res, 11, 1375-1381.  
10673430 G.Schneider, H.Käck, and Y.Lindqvist (2000).
The manifold of vitamin B6 dependent enzymes.
  Structure, 8, R1-R6.  
11193400 H.Inoue, K.Inagaki, N.Adachi, T.Tamura, N.Esaki, K.Soda, and H.Tanaka (2000).
Role of tyrosine 114 of L-methionine gamma-lyase from Pseudomonas putida.
  Biosci Biotechnol Biochem, 64, 2336-2343.  
10212249 C.Steegborn, T.Clausen, P.Sondermann, U.Jacob, M.Worbs, S.Marinkovic, R.Huber, and M.C.Wahl (1999).
Kinetics and inhibition of recombinant human cystathionine gamma-lyase. Toward the rational control of transsulfuration.
  J Biol Chem, 274, 12675-12684.  
10584075 S.Roy (1999).
Multifunctional enzymes and evolution of biosynthetic pathways: retro-evolution by jumps.
  Proteins, 37, 303-309.  
10595588 T.Clausen, M.C.Wahl, A.Messerschmidt, R.Huber, J.C.Fuhrmann, B.Laber, W.Streber, and C.Steegborn (1999).
Cloning, purification and characterisation of cystathionine gamma-synthase from Nicotiana tabacum.
  Biol Chem, 380, 1237-1242.  
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.