PDBsum entry 1qgn

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Lyase PDB id
Protein chains
(+ 2 more) 398 a.a. *
PLP ×8
Waters ×326
* Residue conservation analysis
PDB id:
Name: Lyase
Title: Cystathionine gamma-synthase from nicotiana tabacum
Structure: Protein (cystathionine gamma-synthase). Chain: a, b, c, d, e, f, g, h. Engineered: yes. Other_details: aldimine linkage between pyridoxal 5'-phosph and lys261 nz
Source: Nicotiana tabacum. Common tobacco. Organism_taxid: 4097. Organelle: chloroplast. Gene: metb. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Homo-Tetramer (from PDB file)
2.90Å     R-factor:   0.201     R-free:   0.250
Authors: C.Steegborn,A.Messerschmidt,B.Laber,W.Streber,R.Huber,T.Clau
Key ref:
C.Steegborn et al. (1999). The crystal structure of cystathionine gamma-synthase from Nicotiana tabacum reveals its substrate and reaction specificity. J Mol Biol, 290, 983-996. PubMed id: 10438597 DOI: 10.1006/jmbi.1999.2935
02-May-99     Release date:   25-Aug-99    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q9ZPL5  (Q9ZPL5_TOBAC) -  Cystathionine gamma-synthase
445 a.a.
398 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   1 term 
  Biochemical function     catalytic activity     2 terms  


DOI no: 10.1006/jmbi.1999.2935 J Mol Biol 290:983-996 (1999)
PubMed id: 10438597  
The crystal structure of cystathionine gamma-synthase from Nicotiana tabacum reveals its substrate and reaction specificity.
C.Steegborn, A.Messerschmidt, B.Laber, W.Streber, R.Huber, T.Clausen.
Cystathionine gamma-synthase catalyses the committed step of de novo methionine biosynthesis in micro-organisms and plants, making the enzyme an attractive target for the design of new antibiotics and herbicides. The crystal structure of cystathionine gamma-synthase from Nicotiana tabacum has been solved by Patterson search techniques using the structure of Escherichia coli cystathionine gamma-synthase. The model was refined at 2.9 A resolution to a crystallographic R -factor of 20.1 % (Rfree25.0 %). The physiological substrates of the enzyme, L-homoserine phosphate and L-cysteine, were modelled into the unliganded structure. These complexes support the proposed ping-pong mechanism for catalysis and illustrate the dissimilar substrate specificities of bacterial and plant cystathionine gamma-synthases on a molecular level. The main difference arises from the binding modes of the distal substrate groups (O -acetyl/succinyl versusO -phosphate). Central in fixing the distal phosphate of the plant CGS substrate is an exposed lysine residue that is strictly conserved in plant cystathionine gamma-synthases whereas bacterial enzymes carry a glycine residue at this position. General insight regarding the reaction specificity of transsulphuration enzymes is gained by the comparison to cystathionine beta-lyase from E. coli, indicating the mechanistic importance of a second substrate binding site for L-cysteine which leads to different chemical reaction types.
  Selected figure(s)  
Figure 4.
Figure 4. Modelled complex between tCGS and its substrate HSP. The stereo plot shows the active site of tCGS with the mod- elled external aldimine between HSP and PLP. The crystal structure (blue) with the manually positioned ligand molecule (yellow) is overlaid with the minimised models (ligand: grey; protein: green). The Figure was produced with SETOR (Evans, 1993).
Figure 7.
Figure 7. Schematic drawing illustrating the reaction mechanism proposed for tCGS. After formation of the Michaelis complex (I), trans- aldimination leads to an external aldimine (II); via a carbanionic intermediate (III), a PLP substrate ketimine (IV) is formed. After release of the phosphate leaving group from an a-b-unsaturated intermediate (V), cysteine enters the active site and reacts at C g of the partitioning intermediate (qui- ninoid form of PLP-bound vinyl- glycine, VI). The resulting a-b- unsaturated intermediate (VII) is protonated to form the PLP pro- duct ketimine (VIII). Finally, the product PLP aldimine results from protonation of a carbanionic inter- mediate (IX) by the active site lysine.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1999, 290, 983-996) copyright 1999.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  20019093 G.Jander, and V.Joshi (2010).
Recent progress in deciphering the biosynthesis of aspartate-derived amino acids in plants.
  Mol Plant, 3, 54-65.  
18366663 R.Merkl, and M.Zwick (2008).
H2r: identification of evolutionary important residues by means of an entropy based analysis of multiple sequence alignments.
  BMC Bioinformatics, 9, 151.  
15654104 M.J.Spiering, C.D.Moon, H.H.Wilkinson, and C.L.Schardl (2005).
Gene clusters for insecticidal loline alkaloids in the grass-endophytic fungus Neotyphodium uncinatum.
  Genetics, 169, 1403-1414.  
16307301 M.Wirtz, and M.Droux (2005).
Synthesis of the sulfur amino acids: cysteine and methionine.
  Photosynth Res, 86, 345-362.  
15498941 A.Paiardini, F.Bossa, and S.Pascarella (2004).
Evolutionarily conserved regions and hydrophobic contacts at the superfamily level: The case of the fold-type I, pyridoxal-5'-phosphate-dependent enzymes.
  Protein Sci, 13, 2992-3005.  
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
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.  
11092940 V.Sridhar, M.Xu, Q.Han, X.Sun, Y.Tan, R.M.Hoffman, and G.S.Prasad (2000).
Crystallization and preliminary crystallographic characterization of recombinant L-methionine-alpha-deamino-gamma-mercaptomethane lyase (methioninase).
  Acta Crystallogr D Biol Crystallogr, 56, 1665-1667.  
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