PDBsum entry 2c0a

Go to PDB code: 
protein ligands Protein-protein interface(s) links
Lyase PDB id
Protein chains
213 a.a. *
PO4 ×4
Waters ×737
* Residue conservation analysis
PDB id:
Name: Lyase
Title: Mechanism of the class i kdpg aldolase
Structure: Khg/kdpg aldolase. Chain: a, b, c. Engineered: yes. Mutation: yes
Source: Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 469008.
Biol. unit: Trimer (from PDB file)
1.55Å     R-factor:   0.170     R-free:   0.217
Authors: M.J.Hutchins,S.W.B.Fullerton,E.J.Toone,J.H.Naismith
Key ref: S.W.Fullerton et al. (2006). Mechanism of the Class I KDPG aldolase. Bioorg Med Chem, 14, 3002-3010. PubMed id: 16403639 DOI: 10.1016/j.bmc.2005.12.022
29-Aug-05     Release date:   01-Sep-05    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P0A955  (ALKH_ECOLI) -  KHG/KDPG aldolase
213 a.a.
213 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class 2: E.C.  - 2-dehydro-3-deoxy-phosphogluconate aldolase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 2-dehydro-3-deoxy-6-phosphate-D-gluconate = pyruvate + D-glyceraldehyde 3-phosphate
= pyruvate
D-glyceraldehyde 3-phosphate
Bound ligand (Het Group name = PO4)
matches with 50.00% similarity
   Enzyme class 3: E.C.  - 4-hydroxy-2-oxoglutarate aldolase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 4-hydroxy-2-oxoglutarate = pyruvate + glyoxylate
= pyruvate
+ glyoxylate
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   3 terms 
  Biological process     metabolic process   1 term 
  Biochemical function     catalytic activity     5 terms  


DOI no: 10.1016/j.bmc.2005.12.022 Bioorg Med Chem 14:3002-3010 (2006)
PubMed id: 16403639  
Mechanism of the Class I KDPG aldolase.
S.W.Fullerton, J.S.Griffiths, A.B.Merkel, M.Cheriyan, N.J.Wymer, M.J.Hutchins, C.A.Fierke, E.J.Toone, J.H.Naismith.
In vivo, 2-keto-3-deoxy-6-phosphogluconate (KDPG) aldolase catalyzes the reversible, stereospecific retro-aldol cleavage of KDPG to pyruvate and D-glyceraldehyde-3-phosphate. The enzyme is a lysine-dependent (Class I) aldolase that functions through the intermediacy of a Schiff base. Here, we propose a mechanism for this enzyme based on crystallographic studies of wild-type and mutant aldolases. The three dimensional structure of KDPG aldolase from the thermophile Thermotoga maritima was determined to 1.9A. The structure is the standard alpha/beta barrel observed for all Class I aldolases. At the active site Lys we observe clear density for a pyruvate Schiff base. Density for a sulfate ion bound in a conserved cluster of residues close to the Schiff base is also observed. We have also determined the structure of a mutant of Escherichia coli KDPG aldolase in which the proposed general acid/base catalyst has been removed (E45N). One subunit of the trimer contains density suggesting a trapped pyruvate carbinolamine intermediate. All three subunits contain a phosphate ion bound in a location effectively identical to that of the sulfate ion bound in the T. maritima enzyme. The sulfate and phosphate ions experimentally locate the putative phosphate binding site of the aldolase and, together with the position of the bound pyruvate, facilitate construction of a model for the full-length KDPG substrate complex. The model requires only minimal positional adjustments of the experimentally determined covalent intermediate and bound anion to accommodate full-length substrate. The model identifies the key catalytic residues of the protein and suggests important roles for two observable water molecules. The first water molecule remains bound to the enzyme during the entire catalytic cycle, shuttling protons between the catalytic glutamate and the substrate. The second water molecule arises from dehydration of the carbinolamine and serves as the nucleophilic water during hydrolysis of the enzyme-product Schiff base. The second water molecule may also mediate the base-catalyzed enolization required to form the carbon nucleophile, again bridging to the catalytic glutamate. Many aspects of this mechanism are observed in other Class I aldolases and suggest a mechanistically and, perhaps, evolutionarily related family of aldolases distinct from the N-acetylneuraminate lyase (NAL) family.

Literature references that cite this PDB file's key reference

  PubMed id Reference
19846764 E.W.Debler, R.Müller, D.Hilvert, and I.A.Wilson (2009).
An aspartate and a water molecule mediate efficient acid-base catalysis in a tailored antibody pocket.
  Proc Natl Acad Sci U S A, 106, 18539-18544.
PDB codes: 3fo0 3fo1 3fo2
18081287 J.J.Maresh, L.A.Giddings, A.Friedrich, E.A.Loris, S.Panjikar, B.L.Trout, J.Stöckigt, B.Peters, and S.E.O'Connor (2008).
Strictosidine synthase: mechanism of a Pictet-Spengler catalyzing enzyme.
  J Am Chem Soc, 130, 710-723.
PDB code: 2vaq
18323453 L.Jiang, E.A.Althoff, F.R.Clemente, L.Doyle, D.Röthlisberger, A.Zanghellini, J.L.Gallaher, J.L.Betker, F.Tanaka, C.F.Barbas, D.Hilvert, K.N.Houk, B.L.Stoddard, and D.Baker (2008).
De novo computational design of retro-aldol enzymes.
  Science, 319, 1387-1391.
PDB codes: 3b5l 3b5v 3hoj
18972054 M.Lombardo, S.Easwar, A.De Marco, F.Pasi, and C.Trombini (2008).
A modular approach to catalyst hydrophobicity for an asymmetric aldol reaction in a biphasic aqueous environment.
  Org Biomol Chem, 6, 4224-4229.  
  18997324 Q.Zhang, F.Gao, J.Qi, H.Cheng, Y.Liu, and G.F.Gao (2008).
Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of 2-keto-3-deoxy-6-phosphogluconate (KDPG) aldolase from Streptococcus suis serotype 2.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 997-999.  
17962400 M.Cheriyan, E.J.Toone, and C.A.Fierke (2007).
Mutagenesis of the phosphate-binding pocket of KDPG aldolase enhances selectivity for hydrophobic substrates.
  Protein Sci, 16, 2368-2377.  
17641651 M.J.Walters, and E.J.Toone (2007).
Pyruvate aldolases in chiral carbon-carbon bond formation.
  Nat Protoc, 2, 1825-1830.  
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.