PDBsum entry 1p7t

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protein ligands metals Protein-protein interface(s) links
Lyase PDB id
Jmol PyMol
Protein chains
706 a.a. *
ACO ×2
PYR ×2
PG4 ×2
_MG ×2
Waters ×583
* Residue conservation analysis
PDB id:
Name: Lyase
Title: Structure of escherichia coli malate synthase g:pyruvate:ace coenzyme a abortive ternary complex at 1.95 angstrom resolu
Structure: Malate synthase g. Chain: a. Synonym: msg. Engineered: yes. Mutation: yes. Malate synthase g. Chain: b. Synonym: msg. Engineered: yes.
Source: Escherichia coli str. K12 substr.. Organism_taxid: 316407. Strain: w3110. Gene: glcb or glc or b2976. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.95Å     R-factor:   0.197     R-free:   0.294
Authors: D.M.Anstrom,K.Kallio,S.J.Remington
Key ref:
D.M.Anstrom et al. (2003). Structure of the Escherichia coli malate synthase G:pyruvate:acetyl-coenzyme A abortive ternary complex at 1.95 A resolution. Protein Sci, 12, 1822-1832. PubMed id: 12930982 DOI: 10.1110/ps.03174303
05-May-03     Release date:   09-Sep-03    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P37330  (MASZ_ECOLI) -  Malate synthase G
723 a.a.
706 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 = ACO)
corresponds exactly
+ H(2)O
Bound ligand (Het Group name = PYR)
matches with 83.33% 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   2 terms 
  Biological process     glyoxylate cycle   3 terms 
  Biochemical function     catalytic activity     5 terms  


DOI no: 10.1110/ps.03174303 Protein Sci 12:1822-1832 (2003)
PubMed id: 12930982  
Structure of the Escherichia coli malate synthase G:pyruvate:acetyl-coenzyme A abortive ternary complex at 1.95 A resolution.
D.M.Anstrom, K.Kallio, S.J.Remington.
Malate synthase, an enzyme of the glyoxylate pathway, catalyzes the condensation and subsequent hydrolysis of acetyl-coenzyme A (acetyl-CoA) and glyoxylate to form malate and CoA. In the present study, we present the 1.95 A-resolution crystal structure of Escherichia coli malate synthase isoform G in complex with magnesium, pyruvate, and acetyl-CoA, and we compare it with previously determined structures of substrate and product complexes. The results reveal how the enzyme recognizes and activates the substrate acetyl-CoA, as well as conformational changes associated with substrate binding, which may be important for catalysis. On the basis of these results and mutagenesis of active site residues, Asp 631 and Arg 338 are proposed to act in concert to form the enolate anion of acetyl-CoA in the rate-limiting step. The highly conserved Cys 617, which is immediately adjacent to the presumed catalytic base Asp 631, appears to be oxidized to cysteine-sulfenic acid. This can explain earlier observations of the susceptibility of the enzyme to inactivation and aggregation upon X-ray irradiation and indicates that cysteine oxidation may play a role in redox regulation of malate synthase activity in vivo. There is mounting evidence that enzymes of the glyoxylate pathway are virulence factors in several pathogenic organisms, notably Mycobacterium tuberculosis and Candida albicans. The results described in this study add insight into the mechanism of catalysis and may be useful for the design of inhibitory compounds as possible antimicrobial agents.
  Selected figure(s)  
Figure 1.
Figure 1. Ribbon diagram of malate synthase. Domains are indicated by color: N-terminal -helical clasp (blue), extended surface loop linker (turquoise), TIM barrel (red), / domain (yellow), and C-terminal plug (purple). Magnesium, pyruvate, and acetyl-coenzyme A are shown in green ball-and-stick form.
Figure 4.
Figure 4. Proposed catalytic mechanism of malate synthase G, adapted from Howard et al. (2000).
  The above figures are reprinted by permission from the Protein Society: Protein Sci (2003, 12, 1822-1832) copyright 2003.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20633347 D.Sheppard, R.Sprangers, and V.Tugarinov (2010).
Experimental approaches for NMR studies of side-chain dynamics in high-molecular-weight proteins.
  Prog Nucl Magn Reson Spectrosc, 56, 1.  
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.  
19549344 B.Roucourt, N.Minnebo, P.Augustijns, K.Hertveldt, G.Volckaert, and R.Lavigne (2009).
Biochemical characterization of malate synthase G of P. aeruginosa.
  BMC Biochem, 10, 20.  
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.  
19776021 S.L.Bulfer, E.M.Scott, J.F.Couture, L.Pillus, and R.C.Trievel (2009).
Crystal structure and functional analysis of homocitrate synthase, an essential enzyme in lysine biosynthesis.
  J Biol Chem, 284, 35769-35780.
PDB codes: 3ivs 3ivt 3ivu
18008171 A.Grishaev, V.Tugarinov, L.E.Kay, J.Trewhella, and A.Bax (2008).
Refined solution structure of the 82-kDa enzyme malate synthase G from joint NMR and synchrotron SAXS restraints.
  J Biomol NMR, 40, 95.
PDB code: 2jqx
18227433 F.R.Salsbury, S.T.Knutson, L.B.Poole, and J.S.Fetrow (2008).
Functional site profiling and electrostatic analysis of cysteines modifiable to cysteine sulfenic acid.
  Protein Sci, 17, 299-312.  
18714089 J.R.Lohman, A.C.Olson, and S.J.Remington (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.
PDB codes: 3cux 3cuz 3cv1 3cv2
18234830 K.Kubiak, and W.Nowak (2008).
Molecular dynamics simulations of the photoactive protein nitrile hydratase.
  Biophys J, 94, 3824-3838.  
17577419 K.Singh, and V.Bhakuni (2007).
Cation induced differential effect on structural and functional properties of Mycobacterium tuberculosis alpha-isopropylmalate synthase.
  BMC Struct Biol, 7, 39.  
16601870 C.Mir, E.Lopez-Viñas, R.Aledo, B.Puisac, C.Rizzo, C.Dionisi-Vici, F.Deodato, J.Pié, P.Gomez-Puertas, F.G.Hegardt, and N.Casals (2006).
A single-residue mutation, G203E, causes 3-hydroxy-3-methylglutaric aciduria by occluding the substrate channel in the 3D structural model of HMG-CoA lyase.
  J Inherit Metab Dis, 29, 64-70.  
16877713 D.M.Anstrom, and S.J.Remington (2006).
The product complex of M. tuberculosis malate synthase revisited.
  Protein Sci, 15, 2002-2007.
PDB code: 2gq3
16846242 Carvalho, and J.S.Blanchard (2006).
Kinetic and chemical mechanism of alpha-isopropylmalate synthase from Mycobacterium tuberculosis.
  Biochemistry, 45, 8988-8999.  
  16511237 D.M.Anstrom, L.Colip, B.Moshofsky, E.Hatcher, and S.J.Remington (2005).
Systematic replacement of lysine with glutamine and alanine in Escherichia coli malate synthase G: effect on crystallization.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 61, 1069-1074.  
16075427 V.Tugarinov, and L.E.Kay (2005).
Methyl groups as probes of structure and dynamics in NMR studies of high-molecular-weight proteins.
  Chembiochem, 6, 1567-1577.  
15637152 V.Tugarinov, W.Y.Choy, V.Y.Orekhov, and L.E.Kay (2005).
Solution NMR-derived global fold of a monomeric 82-kDa enzyme.
  Proc Natl Acad Sci U S A, 102, 622-627.
PDB code: 1y8b
15159544 N.Koon, C.J.Squire, and E.N.Baker (2004).
Crystal structure of LeuA from Mycobacterium tuberculosis, a key enzyme in leucine biosynthesis.
  Proc Natl Acad Sci U S A, 101, 8295-8300.
PDB codes: 1sr9 3fig
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.