User:Iarcher45/sandbox1
| 3-dehydroquinate dehydratase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 The third step of the Shikimate Pathway is catalyzed by DHQD | |||||||||
| Identifiers | |||||||||
| EC no. | 4.2.1.10 | ||||||||
| CAS no. | 9012-66-2 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
| |||||||||
| Type I 3-dehydroquinase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 The structure of type i 3-dehydroquinate dehydratase from salmonella typhi | |||||||||
| Identifiers | |||||||||
| Symbol | DHquinase_I | ||||||||
| Pfam | PF01487 | ||||||||
| Pfam clan | CL0036 | ||||||||
| InterPro | IPR001381 | ||||||||
| PROSITE | PDOC00789 | ||||||||
| SCOP2 | 2dhq / SCOPe / SUPFAM | ||||||||
| |||||||||
| Dehydroquinase class II | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | DHquinase_II | ||||||||
| Pfam | PF01220 | ||||||||
| PROSITE | PDOC00789 | ||||||||
| SCOP2 | 2dhq / SCOPe / SUPFAM | ||||||||
| |||||||||
Overview: 3-Dehydroquinate Dehydratase and the Shikimate Pathway
[edit]3-Dehydroquinate Dehydratase is an enzyme that catalyzes the third step of the Shikimate Pathway. The Shikimate pathway is a biosynthetic pathway that allows plants, fungi, and bacteria to produce aromatic amino acids. [1] Mammals do not have this pathway, meaning that they must obtain these essential amino acids through their diet. Aromatic Amino acids include Phenylalanine, Tyrosine, and Tryptophan. [2]
In enzymology, a 3-dehydroquinate dehydratase (EC 4.2.1.10) is an enzyme that catalyzes the chemical reaction
- 3-dehydroquinate 3-dehydroshikimate + H2O
Hence, this enzyme has one substrate, 3-dehydroquinate, and two products, 3-dehydroshikimate and H2O.
This enzyme dehydrates 3-Dehydroquinate, converting it to 3-Dehydroshikimate, as indicated in the diagram on the right. This is the third step in the Shikimate pathway. It belongs to the family of lyases, specifically the hydro-lyases, which cleave carbon-oxygen bonds. The systematic name of this enzyme class is 3-dehydroquinate hydro-lyase (3-dehydroshikimate-forming). This enzyme is one of the few examples of convergent evolution. The two separate versions of this enzyme have different amino acid sequences. [3]
3-Dehydroquinate dehydratase is also commonly referred to as Dehydroquinate dehydratase and DHQD. Other names include 3-dehydroquinate hydrolase, DHQase, 3-dehydroquinase, 5-dehydroquinase, dehydroquinase, 5-dehydroquinate dehydratase, 5-dehydroquinate hydro-lyase, and 3-dehydroquinate hydro-lyase. [4]
Discovery of the Shikimate Pathway
[edit]The Shikimate Pathway was determined to be a major biosynthetic route for the production of aromatic amino acids through the research of Bernhard Davis and David Sprinson. [5]
Enzymatic Background and Evolutionary Origins
[edit]Purposes of the products of the Shikimate Acid Pathway
[edit]The aromatic amino acids produced by the Shikimate Acid Pathway are used by higher plants as protein building blocks and as precursors for several secondary metabolites. Examples of such secondary metabolites are plant pigments and compounds to defend against herbivores, insects, and UV light. The specific aromatic secondary metabolites produced, as well as when and in what quantities they are produced in, varies across different types of plants. Mammals consume essential amino acids in their diets, converting them to precursors for important substances such as neurotransmitters.
Convergent Evolution: Two Types of 3-Dehydroquinate Dehydratase
[edit]As mentioned previously, two classes of 3-Dehydroquinate Dehydratase exist, known as types I and II. These two versions have different amino acid sequences and different secondary structures. Type I is present in fungi, plants, and some bacteria, for the biosynthesis of chorismate. It catalyzes the cis-dehydration of 3-Dehydroquinate thru a covalent imine intermediate. Type I is heat liable and has Km values in the low micromolar range. Type II is present in the quinate pathway of fungi and the shikimate pathway of most bacteria. It catalyzes a trans-dehydration using an enolate intermediate. It is heat stable and has Km values one or two orders of magnitude higher than the Type I Km values. [6]
The best studied type I enzyme is from Escherichia coli (gene aroD) and related bacteria. It is a homodimeric protein. In fungi, dehydroquinase is part of a multifunctional enzyme which catalyses five consecutive steps in the shikimate pathway. A histidine is involved in the catalytic mechanism.[7]
Other purposes for DHQD
[edit]3-Dehydroquinate Dehydratase is also an enzyme present in the process of the degradation of quinate. Both 3-Dehydroquinate and 3-Dehydroshikimate are intermediates in the reaction mechanism. The following image shows this process in Quinate Degradation. [8]
Structural studies
[edit]As of late 2007, 26 structures have been solved for this class of enzymes, with PDB accession codes 1D0I, 1GQN, 1GQO, 1GTZ, 1GU0, 1GU1, 1H05, 1H0R, 1H0S, 1J2Y, 1L9W, 1QFE, 1SFJ, 1SFL, 1UQR, 1V1J, 2BT4, 2C4V, 2C4W, 2C57, 2CJF, 2DHQ, 2EGZ, 2GPT, 2OCZ, and 2YR1.
Recent and Current Research
[edit]The Shikimate pathway has become a focus of research into the development of herbicides and antimicrobial agents because it is an essential pathway in many plants, bacteria, and parasites but does not exist in mammals. [9]
Recent research at the University of Cambridge and Texas A&M has been focused on the potential for drugs targeted at the Shikimate pathway in Mycobacterium tuberculosis. They hope to inhibit the DHQD enzyme, thereby preventing individuals from becoming infected with tuberculosis. [10]
Studies have determined that most of the 3-Dehydroquinate-Dehydratase in bacteria and higher plants is Type I DHQD. Through further studies scientists hope to be able to analyze both Type I and Type II crystals to determine if there are any fundamental differences in the reaction mechanisms of these two types of DHQD. [11]
References
[edit]- ^ {Cite CAS|9012-66-2}}
- ^ {Cite pmcid|PMC160886}}
- ^ {Cite CAS|9012-66-2}}
- ^ {Cite CAS|9012-66-2}}
- ^ {Cite pmcid|PMC160886}}
- ^ {Cite pmcid|PMC160886}}
- ^ Deka RK, Kleanthous C, Coggins JR (November 1992). "Identification of the essential histidine residue at the active site of Escherichia coli dehydroquinase". J. Biol. Chem. 267 (31): 22237–42. doi:10.1016/S0021-9258(18)41660-2. PMID 1429576.
{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link) - ^ {Cite pmcid|PMC160886}}
- ^ {Cite pmcid|PMC160886}}
- ^ {Cite doi|10.1042}}
- ^ {Cite pmcid|PMC160886}}
Further reading
[edit]- MITSUHASHI S, DAVIS BD (1954). "Aromatic biosynthesis. XII. Conversion of 5-dehydroquinic acid to 5-dehydroshikimic acid dy 5-dehydroquinase". Biochim. Biophys. Acta. 15 (1): 54–61. doi:10.1016/0006-3002(54)90093-1. PMID 13198937.
- MITSUHASHI S, DAVIS BD (1954). "Aromatic biosynthesis. XIII. Conversion of quinic acid to 5-dehydroquinic acid by quinic dehydrogenase". Biochim. Biophys. Acta. 15 (2): 268–80. doi:10.1016/0006-3002(54)90069-4. PMID 13208693.