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PDBsum entry 1nal

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protein ligands Protein-protein interface(s) links
Lyase PDB id
1nal
Jmol
Contents
Protein chains
291 a.a. *
Ligands
SO4 ×4
Waters ×60
* Residue conservation analysis
PDB id:
1nal
Name: Lyase
Title: The three-dimensional structure of n-acetylneuraminate lyase from escherichia coli
Structure: N-acetylneuraminate lyase. Chain: 1, 2, 3, 4. Ec: 4.1.3.3
Source: Escherichia coli. Organism_taxid: 562
Biol. unit: Tetramer (from PQS)
Resolution:
2.20Å     R-factor:   0.208    
Authors: T.Izard,M.C.Lawrence,R.L.Malby,G.G.Lilley,P.M.Colman
Key ref:
T.Izard et al. (1994). The three-dimensional structure of N-acetylneuraminate lyase from Escherichia coli. Structure, 2, 361-369. PubMed id: 8081752 DOI: 10.1016/S0969-2126(00)00038-1
Date:
28-Feb-94     Release date:   15-Sep-95    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P0A6L4  (NANA_ECOLI) -  N-acetylneuraminate lyase
Seq:
Struc:
297 a.a.
291 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.4.1.3.3  - N-acetylneuraminate lyase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: N-acetylneuraminate = N-acetyl-D-mannosamine + pyruvate
N-acetylneuraminate
= N-acetyl-D-mannosamine
+ pyruvate
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   3 terms 
  Biochemical function     catalytic activity     4 terms  

 

 
    reference    
 
 
DOI no: 10.1016/S0969-2126(00)00038-1 Structure 2:361-369 (1994)
PubMed id: 8081752  
 
 
The three-dimensional structure of N-acetylneuraminate lyase from Escherichia coli.
T.Izard, M.C.Lawrence, R.L.Malby, G.G.Lilley, P.M.Colman.
 
  ABSTRACT  
 
BACKGROUND: N-acetylneuraminate lyase catalyzes the cleavage of N-acetylneuraminic acid (sialic acid) to form pyruvate and N-acetyl-D-mannosamine. The enzyme plays an important role in the regulation of sialic acid metabolism in bacteria. The reverse reaction can be exploited for the synthesis of sialic acid and some of its derivatives. RESULTS: The structure of the enzyme from Escherichia coli has been determined to 2.2 A resolution by X-ray crystallography. The enzyme is shown to be a tetramer, in which each subunit consists of an alpha/beta-barrel domain followed by a carboxy-terminal extension of three alpha-helices. CONCLUSIONS: The active site of the enzyme is tentatively identified as a pocket at the carboxy-terminal end of the eight-stranded beta-barrel. Lys165 lies within this pocket and is probably the reactive residue which forms a Schiff base intermediate with the substrate. The sequence of N-acetylneuraminate lyase has similarities to those of dihydrodipicolinate synthase and MosA (an enzyme implicated in rhizopine synthesis) suggesting that these last two enzymes share a similar structure to N-acetylneuraminate lyase.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Stereo Cα trace of the Neu5Ac lyase monomer, viewed down the β -barrel axis from its carboxy-terminal end. Every tenth Cα is labelled. Figure 2. Stereo Cα trace of the Neu5Ac lyase monomer, viewed down the β -barrel axis from its carboxy-terminal end. Every tenth Cα is labelled. (Figure produced using MOLSCRIPT [[3]10].)
Figure 3.
Figure 3. Schematic drawing of the secondary structural elements of Neu5Ac lyase viewed down the β -barrel axis from its carboxy- terminal end. The putative catalytic residue Lys165 (see text) is shown in ball-and-stick representation. Figure 3. Schematic drawing of the secondary structural elements of Neu5Ac lyase viewed down the β -barrel axis from its carboxy- terminal end. The putative catalytic residue Lys165 (see text) is shown in ball-and-stick representation. (Figure produced using MOLSCRIPT [[3]10].)
 
  The above figures are reprinted by permission from Cell Press: Structure (1994, 2, 361-369) copyright 1994.  
  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
19057931 H.Y.Chu, Q.C.Zheng, Y.S.Zhao, and H.X.Zhang (2009).
Homology modeling and molecular dynamics study on N-acetylneuraminate lyase.
  J Mol Model, 15, 323-328.  
  19923724 I.Campeotto, S.B.Carr, C.H.Trinh, A.S.Nelson, A.Berry, S.E.Phillips, and A.R.Pearson (2009).
Structure of an Escherichia coli N-acetyl-D-neuraminic acid lyase mutant, E192N, in complex with pyruvate at 1.45 angstrom resolution.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 1088-1090.
PDB code: 2wkj
18625334 A.Buschiazzo, and P.M.Alzari (2008).
Structural insights into sialic acid enzymology.
  Curr Opin Chem Biol, 12, 565-572.  
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 4ptn
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.  
  17565178 N.Shimada, B.Mikami, S.Watanabe, and K.Makino (2007).
Preliminary crystallographic analysis of L-2-keto-3-deoxyarabonate dehydratase, an enzyme involved in an alternative bacterial pathway of L-arabinose metabolism.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 393-395.  
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
15734325 H.H.Huang, H.K.Liao, Y.J.Chen, T.S.Hwang, Y.H.Lin, and C.H.Lin (2005).
Structural characterization of sialic acid synthase by electrospray mass spectrometry--a tetrameric enzyme composed of dimeric dimers.
  J Am Soc Mass Spectrom, 16, 324-332.  
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.  
11342129 N.Wymer, L.V.Buchanan, D.Henderson, N.Mehta, C.H.Botting, L.Pocivavsek, C.A.Fierke, E.J.Toone, and J.H.Naismith (2001).
Directed evolution of a new catalytic site in 2-keto-3-deoxy-6-phosphogluconate aldolase from Escherichia coli.
  Structure, 9, 1-9.
PDB codes: 1fq0 1fwr
10760259 A.Karlstrom, G.Zhong, C.Rader, N.A.Larsen, A.Heine, R.Fuller, B.List, F.Tanaka, I.A.Wilson, C.F.Barbas, and R.A.Lerner (2000).
Using antibody catalysis to study the outcome of multiple evolutionary trials of a chemical task.
  Proc Natl Acad Sci U S A, 97, 3878-3883.  
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.  
10844695 E.Vimr, C.Lichtensteiger, and S.Steenbergen (2000).
Sialic acid metabolism's dual function in Haemophilus influenzae.
  Mol Microbiol, 36, 1113-1123.  
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.  
10903950 M.K.Safo, I.Mathews, F.N.Musayev, M.L.di Salvo, D.J.Thiel, D.J.Abraham, and V.Schirch (2000).
X-ray structure of Escherichia coli pyridoxine 5'-phosphate oxidase complexed with FMN at 1.8 A resolution.
  Structure, 8, 751-762.
PDB code: 1dnl
10921867 T.Izard, and N.C.Blackwell (2000).
Crystal structures of the metal-dependent 2-dehydro-3-deoxy-galactarate aldolase suggest a novel reaction mechanism.
  EMBO J, 19, 3849-3856.
PDB codes: 1dxe 1dxf
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
9255062 A.Marchler-Bauer, and S.H.Bryant (1997).
A measure of success in fold recognition.
  Trends Biochem Sci, 22, 236-240.  
9016724 J.C.Eads, D.Ozturk, T.B.Wexler, C.Grubmeyer, and J.C.Sacchettini (1997).
A new function for a common fold: the crystal structure of quinolinic acid phosphoribosyltransferase.
  Structure, 5, 47-58.
PDB code: 1qap
9388188 P.C.Babbitt, and J.A.Gerlt (1997).
Understanding enzyme superfamilies. Chemistry As the fundamental determinant in the evolution of new catalytic activities.
  J Biol Chem, 272, 30591-30594.  
9204286 Y.Lindqvist, and G.Schneider (1997).
Circular permutations of natural protein sequences: structural evidence.
  Curr Opin Struct Biol, 7, 422-427.  
  8839979 G.Reuter, and H.J.Gabius (1996).
Sialic acids structure-analysis-metabolism-occurrence-recognition.
  Biol Chem Hoppe Seyler, 377, 325-342.  
8805555 J.Jia, W.Huang, U.Schörken, H.Sahm, G.A.Sprenger, Y.Lindqvist, and G.Schneider (1996).
Crystal structure of transaldolase B from Escherichia coli suggests a circular permutation of the alpha/beta barrel within the class I aldolase family.
  Structure, 4, 715-724.
PDB code: 1onr
8920014 K.C.Meysick, K.Dimock, and G.E.Garber (1996).
Molecular characterization and expression of a N-acetylneuraminate lyase gene from Trichomonas vaginalis.
  Mol Biochem Parasitol, 76, 289-292.  
  8828820 R.Schauer, and M.Wember (1996).
Isolation and characterization of sialate lyase from pig kidney.
  Biol Chem Hoppe Seyler, 377, 293-299.  
8939754 S.J.Cooper, G.A.Leonard, S.M.McSweeney, A.W.Thompson, J.H.Naismith, S.Qamar, A.Plater, A.Berry, and W.N.Hunter (1996).
The crystal structure of a class II fructose-1,6-bisphosphate aldolase shows a novel binuclear metal-binding active site embedded in a familiar fold.
  Structure, 4, 1303-1315.
PDB code: 1zen
  8762144 S.Janecek (1996).
Invariant glycines and prolines flanking in loops the strand beta 2 of various (alpha/beta)8-barrel enzymes: a hidden homology?
  Protein Sci, 5, 1136-1143.  
  7592358 J.Martinez, S.Steenbergen, and E.Vimr (1995).
Derived structure of the putative sialic acid transporter from Escherichia coli predicts a novel sugar permease domain.
  J Bacteriol, 177, 6005-6010.  
  8770367 M.W.Parker (1995).
Protein crystallography in Australia.
  Aust N Z J Med, 25, 876-882.  
  7549888 S.Janecek (1995).
Similarity of different beta-strands flanked in loops by glycines and prolines from distinct (alpha/beta)8-barrel enzymes: chance or a homology?
  Protein Sci, 4, 1239-1242.  
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.

 

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