3-dehydroquinate synthase

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3-dehydroquinate synthase
3-dehydroquinate synthase
Ribbon model of the 3-dehydroquinate synthase of Helicobacter pylori , according to PDB  3CLH
other names

DHQ synthase

Existing structure data : PDB  5EKS , PDB  3ZOK , PDB  1DQS

Mass / length primary structure 362 amino acids , 38,881 Da
Secondary to quaternary structure Monomer, dimer, homodimer
Cofactor NAD +
Identifier
Gene name (s) aroB (E. coli)
External IDs
Enzyme classification
EC, category 4.2.3.4 ,  lyase
Response type Cyclization
Substrate 3-deoxyarabinoheptulosanate-7-phosphate
Products 3-dehydroquinate + P i
Occurrence
Homology family HOG000007970
Parent taxon Bacteria , Eukaryota
Orthologue (E. coli)
Entrez 947927
UniProt P07639
Refseq (protein) NP_417848.1
PubMed search 947927

3-Dehydroquinate synthase is an enzyme that mostly degenerates in bacteria , but also in eukaryotes and archaea . It catalyzes the second reaction step of the shikimic acid pathway . In this case, 3-Desoxyarabinoheptulosanat 7-phosphate to 3-dehydroquinate cyclized .

properties

In plants and microorganisms, the shikimic acid pathway enzymes are important for the production of the three aromatic amino acids . In 1970, SL Rotenberg and DB Sprinson, together with Turner et al . (1975) describe the exact reaction mechanism. The catalysis takes place in the enzyme with the help of multi-stage reaction mechanisms, u. a. alcohol oxidation, β-phosphate elimination, carbonyl reduction, ring opening and intramolecular aldol condensation . In some organisms, it forms a multi-enzyme complex , which as AROM complex is known. This complex is a pentafunctional polypeptide that can catalyze several steps in the shikimic acid pathway.

Reaction mechanism

Reaction mechanism of 3-dehydroquinate synthase.svg

use

The DHQ synthases from Xanthomonas oryzae and Helicobacter pylori are of particular importance for drug development . The enzyme from X. oryzae can be used as a potential antibiotic target , whereas in H. pylori the enzyme can act as a potential antimicrobial and antiparasitic agent and herbicide . In medicine, the enzyme from Mycobacterium tuberculosis is used as a target for the treatment of tuberculosis .

Individual evidence

  1. ↑ SL Rotenberg, DB Sprinson: Mechanism and stereochemistry of 5-dehydroquinate synthetase. In: Proceedings of the National Academy of Sciences . Volume 67, Number 4, December 1970, pp. 1669-1672, PMID 5275368 , PMC 283410 (free full text).
  2. ↑ L. Negron, ML Patchett, EJ Parker: Expression, Purification, and Characterization of Dehydroquinate Synthase from Pyrococcus furiosus. In: Enzyme research. Volume 2011, 2011, p. 134893, doi : 10.4061 / 2011/134893 , PMID 21603259 , PMC 3092513 (free full text).
  3. ↑ PT Ngo, S. Natarajan, H. Kim, HK Hung, JG Kim, BM Lee, YJ Ahn, LW Kang: Cloning, expression, crystallization and preliminary X-ray crystallographic analysis of 3-dehydroquinate synthase, Xoo1243, from Xanthomonas oryzae pv. oryzae. In: Acta crystallographica. Section F, Structural biology and crystallization communications. Volume 64, Pt 12 December 2008, pp. 1128–1131, doi : 10.1107 / S1744309108033575 , PMID 19052366 , PMC 2593707 (free full text).
  4. ↑ JS Liu, WC Cheng, HJ Wang, YC Chen, WC Wang: Structure-based inhibitor discovery of Helicobacter pylori dehydroquinate synthase. In: Biochemical and biophysical research communications. Volume 373, Number 1, August 2008, pp. 1-7, doi : 10.1016 / j.bbrc.2008.05.070 , PMID 18503755 .
  5. ↑ JD de Mendonça, F. Ely, MS Palma, J. Frazzon, LA Basso, DS Santos: Functional characterization by genetic complementation of aroB-encoded dehydroquinate synthase from Mycobacterium tuberculosis H37Rv and its heterologous expression and purification. In: Journal of bacteriology. Volume 189, Number 17, September 2007, pp. 6246-6252, doi : 10.1128 / JB.00425-07 , PMID 17586643 , PMC 1951933 (free full text).