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Lyase PDB id
1d0i
Jmol
Contents
Protein chains
(+ 6 more) 150 a.a. *
Ligands
PO4 ×16
TRS ×4
Waters ×2023
* Residue conservation analysis
PDB id:
1d0i
Name: Lyase
Title: Crystal structure of type ii dehydroquinase from streptomyces coelicolor complexed with phosphate ions
Structure: Type ii 3-dehydroquinate hydratase. Chain: a, b, c, d, e, f, g, h, i, j, k, l. Engineered: yes
Source: Streptomyces coelicolor. Organism_taxid: 1902. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: streptomyces coelicolor
Biol. unit: Dodecamer (from PQS)
Resolution:
1.80Å     R-factor:   0.176     R-free:   0.223
Authors: A.W.Roszak,T.Krell,I.S.Hunter,J.R.Coggins,A.J.Lapthorn
Key ref:
A.W.Roszak et al. (2002). The structure and mechanism of the type II dehydroquinase from Streptomyces coelicolor. Structure, 10, 493-503. PubMed id: 11937054 DOI: 10.1016/S0969-2126(02)00747-5
Date:
10-Sep-99     Release date:   13-Sep-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P15474  (AROQ_STRCO) -  3-dehydroquinate dehydratase
Seq:
Struc: 		157 a.a.
150 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.4.2.1.10  - 3-dehydroquinate dehydratase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway: 		Shikimate and Chorismate Biosynthesis
      Reaction: 3-dehydroquinate = 3-dehydroshikimate + H2O
3-dehydroquinate
 = 3-dehydroshikimate
 + H(2)O
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     cellular amino acid biosynthetic process   2 terms 
  Biochemical function     lyase activity     2 terms  

 

 
    Added reference    
 
 
DOI no: 10.1016/S0969-2126(02)00747-5 Structure 10:493-503 (2002)
PubMed id: 11937054  
 
 
The structure and mechanism of the type II dehydroquinase from Streptomyces coelicolor.
A.W.Roszak, D.A.Robinson, T.Krell, I.S.Hunter, M.Fredrickson, C.Abell, J.R.Coggins, A.J.Lapthorn.
 
  ABSTRACT  
 
The structure of the type II DHQase from Streptomyces coelicolor has been solved and refined to high resolution in complexes with a number of ligands, including dehydroshikimate and a rationally designed transition state analogue, 2,3-anhydro-quinic acid. These structures define the active site of the enzyme and the role of key amino acid residues and provide snap shots of the catalytic cycle. The resolution of the flexible lid domain (residues 21-31) shows that the invariant residues Arg23 and Tyr28 close over the active site cleft. The tyrosine acts as the base in the initial proton abstraction, and evidence is provided that the reaction proceeds via an enol intermediate. The active site of the structure of DHQase in complex with the transition state analog also includes molecules of tartrate and glycerol, which provide a basis for further inhibitor design.
 
  Selected figure(s)  
 
Figure 8.
Figure 8. A Schematic Diagram of the Proposed Mechanism of Type II DHQases

 
  The above figure is reprinted by permission from Cell Press: Structure (2002, 10, 493-503) copyright 2002.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21275049 A.T.Tran, K.M.Cergol, N.P.West, E.J.Randall, W.J.Britton, S.A.Bokhari, M.Ibrahim, A.J.Lapthorn, and R.J.Payne (2011).
Synthesis and Evaluation of Potent Ene-yne Inhibitors of Type II Dehydroquinases as Tuberculosis Drug Leads.
  ChemMedChem, 6, 262-265.  
21275050 S.Paz, L.Tizón, J.M.Otero, A.L.Llamas-Saiz, G.C.Fox, M.J.van Raaij, H.Lamb, A.R.Hawkins, A.J.Lapthorn, L.Castedo, and C.González-Bello (2011).
Tetrahydrobenzothiophene Derivatives: Conformationally Restricted Inhibitors of Type II Dehydroquinase.
  ChemMedChem, 6, 266-272.  
19816720 A.Kumar, M.I.Siddiqi, and S.Miertus (2010).
New molecular scaffolds for the design of Mycobacterium tuberculosis type II dehydroquinase inhibitors identified using ligand and receptor based virtual screening.
  J Mol Model, 16, 693-712.  
20815012 A.Peón, J.M.Otero, L.Tizón, V.F.Prazeres, A.L.Llamas-Saiz, G.C.Fox, M.J.van Raaij, H.Lamb, A.R.Hawkins, F.Gago, L.Castedo, and C.González-Bello (2010).
Understanding the key factors that control the inhibition of type II dehydroquinase by (2R)-2-benzyl-3-dehydroquinic acids.
  ChemMedChem, 5, 1726-1733.
PDB codes: 2xb8 2xb9
20300652 D.E.Almonacid, E.R.Yera, J.B.Mitchell, and P.C.Babbitt (2010).
Quantitative comparison of catalytic mechanisms and overall reactions in convergently evolved enzymes: implications for classification of enzyme function.
  PLoS Comput Biol, 6, e1000700.  
19856378 V.F.Prazeres, L.Castedo, H.Lamb, A.R.Hawkins, and C.González-Bello (2009).
2-Substituted-3-Dehydroquinic Acids as Potent Competitive Inhibitors of Type II Dehydroquinase.
  ChemMedChem, 4, 1980-1984.  
18200648 C.Sánchez-Sixto, V.F.Prazeres, L.Castedo, S.W.Suh, H.Lamb, A.R.Hawkins, F.J.Cañada, J.Jiménez-Barbero, and C.González-Bello (2008).
Competitive inhibitors of Helicobacter pylori type II dehydroquinase: synthesis, biological evaluation, and NMR studies.
  ChemMedChem, 3, 756-770.  
18094474 K.A.Stewart, D.A.Robinson, and A.J.Lapthorn (2008).
Type II dehydroquinase: molecular replacement with many copies.
  Acta Crystallogr D Biol Crystallogr, 64, 108-118.  
17004270 C.González-Bello, and L.Castedo (2007).
Progress in type II dehydroquinase inhibitors: from concept to practice.
  Med Res Rev, 27, 177-208.  
17068841 M.D.Toscano, R.J.Payne, A.Chiba, O.Kerbarh, and C.Abell (2007).
Nanomolar Inhibition of Type II Dehydroquinase Based on the Enolate Reaction Mechanism.
  ChemMedChem, 2, 101-112.  
17487901 R.J.Payne, A.Riboldi-Tunnicliffe, O.Kerbarh, A.D.Abell, A.J.Lapthorn, and C.Abell (2007).
Design, Synthesis, and Structural Studies on Potent Biaryl Inhibitors of Type II Dehydroquinases.
  ChemMedChem, 2, 1010-1013.
PDB code: 2cjf
17487900 R.J.Payne, F.Peyrot, O.Kerbarh, A.D.Abell, and C.Abell (2007).
Rational Design, Synthesis, and Evaluation of Nanomolar Type II Dehydroquinase Inhibitors.
  ChemMedChem, 2, 1015-1029.  
16952136 V.F.Prazeres, C.Sánchez-Sixto, L.Castedo, A.Canales, F.J.Cañada, J.Jiménez-Barbero, H.Lamb, A.R.Hawkins, and C.González-Bello (2006).
Determination of the bound conformation of a competitive nanomolar inhibitor of mycobacterium tuberculosis type II dehydroquinase by NMR spectroscopy.
  ChemMedChem, 1, 990-996.  
16106291 M.D.Toscano, K.A.Stewart, J.R.Coggins, A.J.Lapthorn, and C.Abell (2005).
Rational design of new bifunctional inhibitors of type II dehydroquinase.
  Org Biomol Chem, 3, 3102-3104.
PDB code: 2bt4
15229896 C.E.Nichols, M.Lockyer, A.R.Hawkins, and D.K.Stammers (2004).
Crystal structures of Staphylococcus aureus type I dehydroquinase from enzyme turnover experiments.
  Proteins, 56, 625-628.
PDB codes: 1sfj 1sfl
14993670 D.Maes, L.A.Gonzalez-Ramirez, J.Lopez-Jaramillo, B.Yu, H.De Bondt, I.Zegers, E.Afonina, J.M.Garcia-Ruiz, and S.Gulnik (2004).
Structural study of the type II 3-dehydroquinate dehydratase from Actinobacillus pleuropneumoniae.
  Acta Crystallogr D Biol Crystallogr, 60, 463-471.
PDB code: 1uqr
12784220 B.I.Lee, J.E.Kwak, and S.W.Suh (2003).
Crystal structure of the type II 3-dehydroquinase from Helicobacter pylori.
  Proteins, 51, 616-617.
PDB code: 1j2y
12637497 G.Michel, A.W.Roszak, V.Sauvé, J.Maclean, A.Matte, J.R.Coggins, M.Cygler, and A.J.Lapthorn (2003).
Structures of shikimate dehydrogenase AroE and its Paralog YdiB. A common structural framework for different activities.
  J Biol Chem, 278, 19463-19472.
PDB codes: 1nyt 1o9b
12624088 J.Benach, I.Lee, W.Edstrom, A.P.Kuzin, Y.Chiang, T.B.Acton, G.T.Montelione, and J.F.Hunt (2003).
The 2.3-A crystal structure of the shikimate 5-dehydrogenase orthologue YdiB from Escherichia coli suggests a novel catalytic environment for an NAD-dependent dehydrogenase.
  J Biol Chem, 278, 19176-19182.
PDB code: 1npd
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.