PDBsum entry 1d8c

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Lyase PDB id
Protein chain
709 a.a. *
SO4 ×5
Waters ×345
* Residue conservation analysis
PDB id:
Name: Lyase
Title: Malate synthase g complexed with magnesium and glyoxylate
Structure: Malate synthase g. Chain: a. Engineered: yes. Mutation: yes. Other_details: c-terminal his-tag (724-731)
Source: Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.00Å     R-factor:   0.177     R-free:   0.270
Authors: B.R.Howard,J.A.Endrizzi,S.J.Remington
Key ref:
B.R.Howard et al. (2000). Crystal structure of Escherichia coli malate synthase G complexed with magnesium and glyoxylate at 2.0 A resolution: mechanistic implications. Biochemistry, 39, 3156-3168. PubMed id: 10715138 DOI: 10.1021/bi992519h
22-Oct-99     Release date:   10-Nov-99    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P37330  (MASZ_ECOLI) -  Malate synthase G
723 a.a.
709 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Malate synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Glyoxylate Cycle
      Reaction: Acetyl-CoA + H2O + glyoxylate = (S)-malate + CoA
+ H(2)O
Bound ligand (Het Group name = GLV)
corresponds exactly
Bound ligand (Het Group name = SOR)
matches with 50.00% similarity
+ 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   3 terms 
  Biochemical function     catalytic activity     4 terms  


DOI no: 10.1021/bi992519h Biochemistry 39:3156-3168 (2000)
PubMed id: 10715138  
Crystal structure of Escherichia coli malate synthase G complexed with magnesium and glyoxylate at 2.0 A resolution: mechanistic implications.
B.R.Howard, J.A.Endrizzi, S.J.Remington.
The crystal structure of selenomethionine-substituted malate synthase G, an 81 kDa monomeric enzyme from Escherichia coli has been determined by MAD phasing, model building, and crystallographic refinement to a resolution of 2.0 A. The crystallographic R factor is 0.177 for 49 242 reflections observed at the incident wavelength of 1.008 A, and the model stereochemistry is satisfactory. The basic fold of the enzyme is that of a beta8/alpha8 (TIM) barrel. The barrel is centrally located, with an N-terminal alpha-helical domain flanking one side. An inserted beta-sheet domain folds against the opposite side of the barrel, and an alpha-helical C-terminal domain forms a plug which caps the active site. Malate synthase catalyzes the condensation of glyoxylate and acetyl-coenzyme A and hydrolysis of the intermediate to yield malate and coenzyme A, requiring Mg(2+). The structure reveals an enzyme-substrate complex with glyoxylate and Mg(2+) which coordinates the aldehyde and carboxylate functions of the substrate. Two strictly conserved residues, Asp631 and Arg338, are proposed to provide concerted acid-base chemistry for the generation of the enol(ate) intermediate of acetyl-coenzyme A, while main-chain hydrogen bonds and bound Mg(2+) polarize glyoxylate in preparation for nucleophilic attack. The catalytic strategy of malate synthase appears to be essentially the same as that of citrate synthase, with the electrophile activated for nucleophilic attack by nearby positive charges and hydrogen bonds, while concerted acid-base catalysis accomplishes the abstraction of a proton from the methyl group of acetyl-coenzyme A. An active site aspartate is, however, the only common feature of these two enzymes, and the active sites of these enzymes are produced by quite different protein folds. Interesting similarities in the overall folds and modes of substrate recognition are discussed in comparisons of malate synthase with pyruvate kinase and pyruvate phosphate dikinase.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20882276 B.E.Alber (2011).
Biotechnological potential of the ethylmalonyl-CoA pathway.
  Appl Microbiol Biotechnol, 89, 17-25.  
21273333 J.Bose, O.Babourina, and Z.Rengel (2011).
Role of magnesium in alleviation of aluminium toxicity in plants.
  J Exp Bot, 62, 2251-2264.  
19957200 C.Guo, and V.Tugarinov (2010).
Selective (1)H- (13)C NMR spectroscopy of methyl groups in residually protonated samples of large proteins.
  J Biomol NMR, 46, 127-133.  
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.  
19002386 C.Guo, and V.Tugarinov (2009).
Identification of HN-methyl NOEs in large proteins using simultaneous amide-methyl TROSY-based detection.
  J Biomol NMR, 43, 21-30.  
19274445 D.Sheppard, C.Guo, and V.Tugarinov (2009).
Methyl-detected 'out-and-back' NMR experiments for simultaneous assignments of Alabeta and Ilegamma2 methyl groups in large proteins.
  J Biomol NMR, 43, 229-238.  
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.  
  19888806 P.F.Zambuzzi-Carvalho, A.H.Cruz, L.K.Santos-Silva, A.M.Goes, C.M.Soares, and M.Pereira (2009).
The malate synthase of Paracoccidioides brasiliensis Pb01 is required in the glyoxylate cycle and in the allantoin degradation pathway.
  Med Mycol, 47, 734-744.  
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
18652454 R.E.London, B.D.Wingad, and G.A.Mueller (2008).
Dependence of amino acid side chain 13C shifts on dihedral angle: application to conformational analysis.
  J Am Chem Soc, 130, 11097-11105.  
17259315 S.Friedmann, B.E.Alber, and G.Fuchs (2007).
Properties of R-citramalyl-coenzyme A lyase and its role in the autotrophic 3-hydroxypropionate cycle of Chloroflexus aurantiacus.
  J Bacteriol, 189, 2906-2914.  
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
16581832 E.Hurtado-Gómez, G.Fernández-Ballester, H.Nothaft, J.Gómez, F.Titgemeyer, and J.L.Neira (2006).
Biophysical characterization of the enzyme I of the Streptomyces coelicolor phosphoenolpyruvate:sugar phosphotransferase system.
  Biophys J, 90, 4592-4604.  
17406304 V.Tugarinov, V.Kanelis, and L.E.Kay (2006).
Isotope labeling strategies for the study of high-molecular-weight proteins by solution NMR spectroscopy.
  Nat Protoc, 1, 749-754.  
  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.  
15687206 M.Meister, S.Saum, B.E.Alber, and G.Fuchs (2005).
L-malyl-coenzyme A/beta-methylmalyl-coenzyme A lyase is involved in acetate assimilation of the isocitrate lyase-negative bacterium Rhodobacter capsulatus.
  J Bacteriol, 187, 1415-1425.  
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
15630560 V.Tugarinov, C.Scheurer, R.Brüschweiler, and L.E.Kay (2004).
Estimates of methyl 13C and 1H CSA values (Deltasigma) in proteins from cross-correlated spin relaxation.
  J Biomol NMR, 30, 397-406.  
15189138 V.Tugarinov, P.M.Hwang, and L.E.Kay (2004).
Nuclear magnetic resonance spectroscopy of high-molecular-weight proteins.
  Annu Rev Biochem, 73, 107-146.  
15756461 V.Tugarinov, W.Y.Choy, E.Kupce, and L.E.Kay (2004).
Addressing the overlap problem in the quantitative analysis of two dimensional NMR spectra: application to (15)N relaxation measurements.
  J Biomol NMR, 30, 347-352.  
12393860 C.V.Smith, C.C.Huang, A.Miczak, D.G.Russell, J.C.Sacchettini, and K.Höner zu Bentrup (2003).
Biochemical and structural studies of malate synthase from Mycobacterium tuberculosis.
  J Biol Chem, 278, 1735-1743.
PDB codes: 1n8i 1n8w
12930982 D.M.Anstrom, K.Kallio, and S.J.Remington (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.
PDB code: 1p7t
12874287 R.L.Tuinstra, and H.M.Miziorko (2003).
Investigation of conserved acidic residues in 3-hydroxy-3-methylglutaryl-CoA lyase: implications for human disease and for functional roles in a family of related proteins.
  J Biol Chem, 278, 37092-37098.  
12489782 A.García-de los Santos, A.Morales, L.Baldomá, S.R.Clark, S.Brom, C.K.Yost, I.Hernández-Lucas, J.Aguilar, and M.F.Hynes (2002).
The glcB locus of Rhizobium leguminosarum VF39 encodes an arabinose-inducible malate synthase.
  Can J Microbiol, 48, 922-932.  
12005052 E.Munir, T.Hattori, and M.Shimada (2002).
Purification and characterization of malate synthase from the glucose-grown wood-rotting basidiomycete Fomitopsis palustris.
  Biosci Biotechnol Biochem, 66, 576-581.  
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.