PDBsum entry 1fdy

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Lyase PDB id
Protein chains
292 a.a. *
3PY ×4
Waters ×171
* Residue conservation analysis
PDB id:
Name: Lyase
Title: N-acetylneuraminate lyase in complex with hydroxypyruvate
Structure: N-acetylneuraminate lyase. Chain: a, b, c, d. Synonym: n-acetylneuraminic acid aldolase. Engineered: yes. Other_details: covalent complex
Source: Escherichia coli. Organism_taxid: 562. Strain: tg1. Gene: npl. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: described in lilley, g.G. Et al. (1992) see reference 2 below
Biol. unit: Tetramer (from PQS)
2.45Å     R-factor:   0.219    
Authors: M.C.Lawrence,J.A.R.G.Barbosa,B.J.Smith,N.E.Hall,P.A.Pilling, H.C.Ooi,S.M.Marcuccio
Key ref:
M.C.Lawrence et al. (1997). Structure and mechanism of a sub-family of enzymes related to N-acetylneuraminate lyase. J Mol Biol, 266, 381-399. PubMed id: 9047371 DOI: 10.1006/jmbi.1996.0769
08-Jul-96     Release date:   22-Oct-97    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P0A6L4  (NANA_ECOLI) -  N-acetylneuraminate lyase
297 a.a.
292 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.  - N-acetylneuraminate lyase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: N-acetylneuraminate = N-acetyl-D-mannosamine + pyruvate
= N-acetyl-D-mannosamine
Bound ligand (Het Group name = 3PY)
matches with 71.00% similarity
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     metabolic process   4 terms 
  Biochemical function     catalytic activity     5 terms  


DOI no: 10.1006/jmbi.1996.0769 J Mol Biol 266:381-399 (1997)
PubMed id: 9047371  
Structure and mechanism of a sub-family of enzymes related to N-acetylneuraminate lyase.
M.C.Lawrence, J.A.Barbosa, B.J.Smith, N.E.Hall, P.A.Pilling, H.C.Ooi, S.M.Marcuccio.
We describe here a sub-family of enzymes related both structurally and functionally to N-acetylneuraminate lyase. Two members of this family (N-acetylneuraminate lyase and dihydrodipicolinate synthase) have known three-dimensional structures and we now proceed to show their structural and functional relationship to two further proteins, trans-o-hydroxybenzylidenepyruvate hydratase-aldolase and D-4-deoxy-5-oxoglucarate dehydratase. These enzymes are all thought to involve intermediate Schiff-base formation with their respective substrates. In order to understand the nature of this intermediate, we have determined the three-dimensional structure of N-acetylneuraminate lyase in complex with hydroxypyruvate (a product analogue) and in complex with one of its products (pyruvate). From these structures we deduce the presence of a closely similar Schiff-base forming motif in all members of the N-acetylneuraminate lyase sub-family. A fifth protein, MosA, is also confirmed to be a member of the sub-family although the involvement of an intermediate Schiff-base in its proposed reaction is unclear.
  Selected figure(s)  
Figure 2.
Figure 2. Diagram of the subunit tertiary structure of N- acetylneuraminate lyase. The b-strands of the (a/b)8 bar- rel are denoted a to h, while the helices are denoted A to H, with the three additional C-terminal helices being denoted I, J, and K, respectively (Izard et al., 1994). The side-chain of Lys165 protrudes into the active site cavity from strand f, and is shown here as complexed to hydroxypyruvate via N z . The Figure was generated using MOLSCRIPT (Kraulis, 1991).
Figure 5.
Figure 5. Conformational detail of the peptide loop formed by residues Ala44 to Glu50 in E. coli NAL and its inter- action with the hydroxypyruvate inhibitor. The peptide loop consists of two type I b-turns comprising residues 45 to 49 and 46 to 50, respectively. Glu50 forms a salt bridge with Lys256 (the latter residue is immediately outside the volume shown). Tyr110 and Tyr111 from a neighbouring monomer also interact with the loop via their O Z atoms. Residues of interest are highlighted in ball-and-stick representation, while surrounding residues are shown in copper- coloured stick-only representation. Hydrogen bonds are shown as yellow lines. The inhibitor (in a 2-deoxy-3-keto form, see the text) is complexed to Lys165 N z via a single bond to C(2), and its carboxylate moiety is positioned so as to make hydrogen bonds with Ser47 N and Thr48 O g1 and Tyr137 O Z . The inhibitor O(3) is capable of forming a hydrogen bond with Tyr137 O Z . A water molecule, coloured red and labelled H2O, is located beyond the inhibitor carboxylate in a pocket in the active site floor. Two other water molecules are also visible; these are located within the protein volume and are not accessible from within the active site cavity. The Figure was generated using MOL- SCRIPT (Kraulis, 1991).
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1997, 266, 381-399) copyright 1997.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20826162 I.Campeotto, A.H.Bolt, T.A.Harman, C.Dennis, C.H.Trinh, S.E.Phillips, A.Nelson, A.R.Pearson, and A.Berry (2010).
Structural insights into substrate specificity in variants of N-acetylneuraminic Acid lyase produced by directed evolution.
  J Mol Biol, 404, 56-69.
PDB codes: 2wnn 2wnq 2wnz 2wo5 2wpb 2xfw
19237310 J.A.Gerlt, and P.C.Babbitt (2009).
Enzyme (re)design: lessons from natural evolution and computation.
  Curr Opin Chem Biol, 13, 10-18.  
18536061 C.P.Phenix, K.Nienaber, P.H.Tam, L.T.Delbaere, and D.R.Palmer (2008).
Structural, functional and calorimetric investigation of MosA, a dihydrodipicolinate synthase from Sinorhizobium meliloti l5-30, does not support involvement in rhizopine biosynthesis.
  Chembiochem, 9, 1591-1602.
PDB code: 2vc6
18754693 J.F.Rakus, A.A.Fedorov, E.V.Fedorov, M.E.Glasner, B.K.Hubbard, J.D.Delli, P.C.Babbitt, S.C.Almo, and J.A.Gerlt (2008).
Evolution of enzymatic activities in the enolase superfamily: L-rhamnonate dehydratase.
  Biochemistry, 47, 9944-9954.
PDB codes: 2i5q 3box 3cxo
18787203 R.C.Dobson, M.D.Griffin, S.R.Devenish, F.G.Pearce, C.A.Hutton, J.A.Gerrard, G.B.Jameson, and M.A.Perugini (2008).
Conserved main-chain peptide distortions: a proposed role for Ile203 in catalysis by dihydrodipicolinate synthase.
  Protein Sci, 17, 2080-2090.
PDB code: 3c0j
18361457 S.Manicka, Y.Peleg, T.Unger, S.Albeck, O.Dym, H.M.Greenblatt, G.Bourenkov, V.Lamzin, S.Krishnaswamy, and J.L.Sussman (2008).
Crystal structure of YagE, a putative DHDPS-like protein from Escherichia coli K12.
  Proteins, 71, 2102-2108.
PDB codes: 2v8z 2v9d
18521592 Y.Li, H.Yu, H.Cao, K.Lau, S.Muthana, V.K.Tiwari, B.Son, and X.Chen (2008).
Pasteurella multocida sialic acid aldolase: a promising biocatalyst.
  Appl Microbiol Biotechnol, 79, 963-970.  
16287120 E.Blagova, V.Levdikov, N.Milioti, M.J.Fogg, A.K.Kalliomaa, J.A.Brannigan, K.S.Wilson, and A.J.Wilkinson (2006).
Crystal structure of dihydrodipicolinate synthase (BA3935) from Bacillus anthracis at 1.94 A resolution.
  Proteins, 62, 297-301.
PDB codes: 1xky 1xl9
16950779 S.Watanabe, N.Shimada, K.Tajima, T.Kodaki, and K.Makino (2006).
Identification and characterization of L-arabonate dehydratase, L-2-keto-3-deoxyarabonate dehydratase, and L-arabinolactonase involved in an alternative pathway of L-arabinose metabolism. Novel evolutionary insight into sugar metabolism.
  J Biol Chem, 281, 33521-33536.  
16041077 R.C.Dobson, M.D.Griffin, G.B.Jameson, and J.A.Gerrard (2005).
The crystal structures of native and (S)-lysine-bound dihydrodipicolinate synthase from Escherichia coli with improved resolution show new features of biological significance.
  Acta Crystallogr D Biol Crystallogr, 61, 1116-1124.
PDB codes: 1yxc 1yxd
15265860 A.Theodossis, H.Walden, E.J.Westwick, H.Connaris, H.J.Lamble, D.W.Hough, M.J.Danson, and G.L.Taylor (2004).
The structural basis for substrate promiscuity in 2-keto-3-deoxygluconate aldolase from the Entner-Doudoroff pathway in Sulfolobus solfataricus.
  J Biol Chem, 279, 43886-43892.
PDB codes: 1w37 1w3i 1w3n 1w3t
12711733 A.C.Joerger, S.Mayer, and A.R.Fersht (2003).
Mimicking natural evolution in vitro: an N-acetylneuraminate lyase mutant with an increased dihydrodipicolinate synthase activity.
  Proc Natl Acad Sci U S A, 100, 5694-5699.
PDB code: 1hl2
11737202 C.Traving, P.Bruse, A.Wächter, and R.Schauer (2001).
The sialate-pyruvate lyase from pig kidney. Elucidation of the primary structure and expression of recombinant enzyme activity.
  Eur J Biochem, 268, 6473-6486.  
11432751 D.Krüger, R.Schauer, and C.Traving (2001).
Characterization and mutagenesis of the recombinant N-acetylneuraminate lyase from Clostridium perfringens: insights into the reaction mechanism.
  Eur J Biochem, 268, 3831-3839.  
11053844 E.J.Hendry, C.L.Buchanan, R.J.Russell, D.W.Hough, C.D.Reeve, M.J.Danson, and G.L.Taylor (2000).
Preliminary crystallographic studies of an extremely thermostable KDG aldolase from Sulfolobus solfataricus.
  Acta Crystallogr D Biol Crystallogr, 56, 1437-1439.  
10732983 M.J.Kiefelt, J.C.Wilson, S.Bennett, M.Gredley, and M.von Itzstein (2000).
Synthesis and evaluation of C-9 modified N-acetylneuraminic acid derivatives as substrates for N-acetylneuraminic acid aldolase.
  Bioorg Med Chem, 8, 657-664.  
10378273 K.Huang, Z.Li, Y.Jia, D.Dunaway-Mariano, and O.Herzberg (1999).
Helix swapping between two alpha/beta barrels: crystal structure of phosphoenolpyruvate mutase with bound Mg(2+)-oxalate.
  Structure, 7, 539-548.
PDB code: 1pym
9667911 W.D.Fessner (1998).
Enzyme mediated C-C bond formation.
  Curr Opin Chem Biol, 2, 85-97.  
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.