PDBsum entry 3cv2

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protein ligands metals Protein-protein interface(s) links
Transferase PDB id
Protein chains
524 a.a. *
OXL ×2
COA ×2
_MG ×3
Waters ×1156
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Atomic resolution structures of escherichia coli and bacillis anthracis malate synthase a: comparison with isoform g and implications for structure based drug design
Structure: Malate synthase a. Chain: a, b. Synonym: msa. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Gene: aceb, mas. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.40Å     R-factor:   0.171     R-free:   0.200
Authors: J.R.Lohman,S.J.Remington
Key ref:
J.R.Lohman et al. (2008). Atomic resolution structures of Escherichia coli and Bacillus anthracis malate synthase A: comparison with isoform G and implications for structure-based drug discovery. Protein Sci, 17, 1935-1945. PubMed id: 18714089 DOI: 10.1110/ps.036269.108
17-Apr-08     Release date:   11-Nov-08    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P08997  (MASY_ECOLI) -  Malate synthase A
533 a.a.
524 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.  - Malate synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Glyoxylate Cycle
      Reaction: Acetyl-CoA + H2O + glyoxylate = (S)-malate + CoA
Bound ligand (Het Group name = COA)
matches with 60.00% similarity
+ H(2)O
Bound ligand (Het Group name = OXL)
matches with 83.00% similarity
= (S)-malate
+ CoA
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     glyoxylate cycle   2 terms 
  Biochemical function     catalytic activity     3 terms  


DOI no: 10.1110/ps.036269.108 Protein Sci 17:1935-1945 (2008)
PubMed id: 18714089  
Atomic resolution structures of Escherichia coli and Bacillus anthracis malate synthase A: comparison with isoform G and implications for structure-based drug discovery.
J.R.Lohman, A.C.Olson, S.J.Remington.
Enzymes of the glyoxylate shunt are important for the virulence of pathogenic organisms such as Mycobacterium tuberculosis and Candida albicans. Two isoforms have been identified for malate synthase, the second enzyme in the pathway. Isoform A, found in fungi and plants, comprises approximately 530 residues, whereas isoform G, found only in bacteria, is larger by approximately 200 residues. Crystal structures of malate synthase isoform G from Escherichia coli and Mycobacterium tuberculosis were previously determined at moderate resolution. Here we describe crystal structures of E. coli malate synthase A (MSA) in the apo form (1.04 A resolution) and in complex with acetyl-coenzyme A and a competitive inhibitor, possibly pyruvate or oxalate (1.40 A resolution). In addition, a crystal structure for Bacillus anthracis MSA at 1.70 A resolution is reported. The increase in size between isoforms A and G can be attributed primarily to an inserted alpha/beta domain that may have regulatory function. Upon binding of inhibitor or substrate, several active site loops in MSA undergo large conformational changes. However, in the substrate bound form, the active sites of isoforms A and G from E. coli are nearly identical. Considering that inhibitors bind with very similar affinities to both isoforms, MSA is as an excellent platform for high-resolution structural studies and drug discovery efforts.
  Selected figure(s)  
Figure 1.
Ternary complex of ecMSA, acetyl-CoA, and inhibitor. (A) Stereo cartoon image of overall structure. TIM barrel (green); C-terminal plug (red); N-terminal clasp (blue). CoA fragment (lavender) and inhibitor (black) shown in ball-and-stick with magnesium as orange sphere. (B) Stereo image of active site inhibitor with omit Fo [minus sign] Fc density contoured at 3[sigma] for the inhibitor, magnesium, and adjacent residues. Black dashes represent hydrogen bonds and red dashes show the presumptive steric clash with pyruvate or an acceptable 2.7 A hydrogen bond to modeled oxalate. Based on structural comparisons with MSG, the blue dashes represent a hypothetical interaction of Asp447 and the terminal methyl group of acetyl-CoA. (C) Stereo image of the CoA binding site with omit Fo [minus sign] Fc density shown at 2[sigma] for CoA and Cys438. The electron density corresponding to the panthothenic acid moiety is too weak to permit a satisfactory model thereof to be constructed. The presumed water molecules at the top, shown interacting with D447, represent the hypothetical location of the terminal acetyl group.
Figure 2.
Schematic diagram of the ecMSA active site with bound inhibitor, indicating atomic distances for intermolecular interactions.
  The above figures are reprinted from an Open Access publication published by the Protein Society: Protein Sci (2008, 17, 1935-1945) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20047909 T.J.Erb, L.Frerichs-Revermann, G.Fuchs, and B.E.Alber (2010).
The apparent malate synthase activity of Rhodobacter sphaeroides is due to two paralogous enzymes, (3S)-Malyl-coenzyme A (CoA)/{beta}-methylmalyl-CoA lyase and (3S)- Malyl-CoA thioesterase.
  J Bacteriol, 192, 1249-1258.  
19684068 M.F.Dunn, J.A.Ramírez-Trujillo, and I.Hernández-Lucas (2009).
Major roles of isocitrate lyase and malate synthase in bacterial and fungal pathogenesis.
  Microbiology, 155, 3166-3175.  
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