Summary: 3-dehydroquinate synthase

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3-dehydroquinate synthase Edit Wikipedia article

3-dehydroquinate synthase

Ribbon representation of the Helicobacter pylori 3-dehydroquinate synthase.^[1]

Identifiers

Databases

PDB structures

AmiGO / EGO

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PubMed	articles
NCBI	proteins

3-dehydroquinate synthase

Identifiers

Symbol

DHQ_synthase

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe
PDBsum	structure summary

In enzymology, a 3-dehydroquinate synthase (EC 4.2.3.4) is an enzyme that catalyzes the chemical reaction

3-deoxy-arabino-heptulosonate 7-phosphate $\rightleftharpoons$ 3-dehydroquinate + phosphate

Hence, this enzyme has one substrate, 3-deoxy-arabino-heptulosonate 7-phosphate, and two products, 3-dehydroquinate and phosphate. The protein uses NAD+ to catalyze the reaction.^[2]^[3] This reaction is part of the shikimate pathway which is involved in the biosynthesis of aromatic amino acids.

3-dehydroquinate synthase belongs to the family of lyases, specifically those carbon-oxygen lyases acting on phosphates. This enzyme participates in phenylalanine, tyrosine and tryptophan biosynthesis. It employs one cofactor, cobalt.

The reaction catalyzed by 3-dehydroquinate synthase

[edit] Background

The shikimate pathway is composed of seven steps, each catalyzed by an enzyme. The shikimate pathway is responsible for producing the precursors for aromatic amino acids, which are essential to our diets because we cannot synthesize them in our bodies. Only plants, bacteria, and microbial eukaryotes are capable of producing aromatic amino acids. The pathway ultimately converts phosphoenolpyruvate and 4-erythrose phosphate into chorismate, the precursor to aromatic amino acids. 3-dehydroquinate synthase is the enzyme that catalyzes reaction in the second step of this pathway. This second step of the reaction eliminates a phosphate from 3-deoxy-D-arabino-heptulosonate 7-phosphate which results in 3-dehydroquinate. 3-dehydroquinate synthase is a monomeric enzyme, and has a molecular weight of 39,000.^[4] 3-dehydroquinate synthase is activated by inorganic phosphate, and requires NAD+ for activity, although the reaction in total is neutral when catalyzed by an enzyme.^[4]

[edit] Function

3-dehydroquinate synthase utilizes a complex multi-step mechanism which includes alcohol oxidation, phosphate b-elimination, carbonyl reduction, ring opening, and intramolecular aldol condensation.^[5] Dehydroquinate synthase requires NAD+ and a cobalt cofactor to catalyze the conversion of 3-deoxy-D-arabino-heptulosonate 7-phosphate into 3-dehydroquinate. In most bacteria, this enzyme has only one function. However, in some organisms, it forms a complex with other enzymes. This complex is known as the AROM complex. The AROM complex is a pentafunctional polypeptide, which contains enzymes that catalyze steps two, three, four, and five of the shikimate pathway.^[5] In addition, dehydroquinate synthase is of particular interest because of its complicated activity relative to its small size.^[5]

[edit] Applications

3-dehydroquinate synthase catalyzes the second step in the shikimate pathway, which is essential for the production of aromatic amino acids in bacteria, plants, and fungi, but not mammals. This makes it an ideal target for new antimicrobial agents, anti-parasitic agents and herbicides.^[1] Other enzymes in the shikimate pathway have already been targeted and put to use as herbicides. Roundup, a common herbicide made by Monsanto, works by inhibiting another enzyme in the shikimate pathway. The shikimate pathway is an ideal choice for herbicides because this pathway does not exist in animals or people so people are not directly affected. Roundup uses an enzyme inhibitor, glyphosphate, to block one of the steps of the shikimate pathway. Glyphosate inhibits 5-enolpyruvylshikimate-3-phosphate synthase (EPSP synthase) which ultimately blocks the production of aromatic amino acids, and without aromatic amino acids, plants cannot survive. However, Monsanto developed a bacterial form of EPSP synthase which was not inhibited by Roundup. Monsanto introduced this gene into plants using agrobacterium and the result was a plant that was resistant to Roundup. This meant that all plants without the bacterial gene would die, leading a much higher degree of weed control.

This cartoon representation of 3-dehydroquinate synthase shows the arrangement of the secondary structure of the protein

3-dehydroquiante synthase interacting with its substrates NAD+, carbaphosphonate, and Zn2+, which are shown as spheres in this representation

This representation of 3-dehydroquinate synthase shows the surface of the enzyme, as well as the active site, which can be seen in the middle.

[edit] Nomenclature

The systematic name of this enzyme class is 3-deoxy-arabino-heptulonate-7-phosphate phosphate-lyase (cyclizing 3-dehydroquinate-forming). Other names in common use include 5-dehydroquinate synthase, 5-dehydroquinic acid synthetase, dehydroquinate synthase, 3-dehydroquinate synthetase, 3-deoxy-arabino-heptulosonate-7-phosphate phosphate-lyase, (cyclizing), and 3-deoxy-arabino-heptulonate-7-phosphate phosphate-lyase (cyclizing).

[edit] References

^ ^a ^b PDB 3CLH; Liu JS, Cheng WC, Wang HJ, Chen YC, Wang WC (2008). "Structure-based inhibitor discovery of Helicobacter pylori dehydroquinate synthase". Biochem. Biophys. Res. Commun. 373 (1): 1â7. doi:10.1016/j.bbrc.2008.05.070. PMID 18503755.; rendered with MacPyMOL
^ Hawkins AR, Lamb HK (August 1995). "The molecular biology of multidomain proteins. Selected examples". Eur. J. Biochem. 232 (1): 7â18. doi:10.1111/j.1432-1033.1995.tb20775.x. PMID 7556173.
^ Barten R, Meyer TF (April 1998). "Cloning and characterisation of the Neisseria gonorrhoeae aroB gene". Mol. Gen. Genet. 258 (1-2): 34â44. PMID 9613570.
^ ^a ^b Herrmann KM, Weaver LM (June 1999). "The Shikimate Pathway". Annu. Rev. Plant Physiol. Plant Mol. Biol. 50: 473â503. doi:10.1146/annurev.arplant.50.1.473. PMID 15012217.
^ ^a ^b ^c Negron L, Patchett ML, Parker EJ (2011). "Expression, Purification, and Characterisation of Dehydroquinate Synthase from Pyrococcus furiosus". Enzyme Res 2011: 134893. doi:10.4061/2011/134893. PMC 3092513. PMID 21603259. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3092513/.

[edit] Further reading

Rotenberg SL, Sprinson DB (1970). "Mechanism and stereochemistry of 5-dehydroquinate synthetase". Proc. Natl. Acad. Sci. U.S.A. 67 (4): 1669â72. doi:10.1073/pnas.67.4.1669. PMC 283410. PMID 5275368. //www.ncbi.nlm.nih.gov/pmc/articles/PMC283410/.
Srinivasan PR, Rothschild J, Sprinson DB (1963). "the enzymic conversion of 3-deoxy-d-arabino-heptulosonic acid 7-phosphate to 5-dehydroquinate". J. Biol. Chem. 238: 3176â82. PMID 14085358.
Bender SL, Mehdi S, Knowles JR (1989). "Dehydroquinate synthase: the role of divalent metal cations and of nicotinamide adenine dinucleotide in catalysis". Biochemistry. 28 (19): 7555â60. doi:10.1021/bi00445a009. PMID 2514789.
Carpenter EP, Hawkins AR, Frost JW, Brown KA (1998). "Structure of dehydroquinate synthase reveals an active site capable of multistep catalysis". Nature. 394 (6690): 299â302. doi:10.1038/28431. PMID 9685163.

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The 3-dehydroquinate synthase EC:4.6.1.3 domain is present in isolation in various bacterial 3-dehydroquinate synthases and also present as a domain in the pentafunctional AROM polypeptide P07547 [2]. 3-dehydroquinate (DHQ) synthase catalyses the formation of dehydroquinate (DHQ) and orthophosphate from 3-deoxy-D-arabino heptulosonic 7 phosphate [1]. This reaction is part of the shikimate pathway which is involved in the biosynthesis of aromatic amino acids.

Literature references

Barten R, Meyer TF; , Mol Gen Genet 1998;258:34-44.: Cloning and characterisation of the Neisseria gonorrhoeae aroB gene. PUBMED:9613570 EPMC:9613570
Hawkins AR, Lamb HK; , Eur J Biochem 1995;232:7-18.: The molecular biology of multidomain proteins. Selected examples. PUBMED:7556173 EPMC:7556173

External database links

PANDIT:	PF01761
Pseudofam:	PF01761
SCOP:	1dqs
SYSTERS:	DHQ_synthase

This tab holds annotation information from the InterPro database.

No InterPro data for this Pfam family.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan DHQS (CL0224), which contains the following 3 members:

DHQ_synthase Fe-ADH Fe-ADH_2

Alignments

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RP15/RP35/RP55/RP75: Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
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	Seed (95)	Full (4669)	Representative proteomes				NCBI (3985)	Meta (3068)
	Seed (95)	Full (4669)	RP15 (401)	RP35 (765)	RP55 (1004)	RP75 (1160)	NCBI (3985)	Meta (3068)
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¹Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: available, not generated, — not available.

Format an alignment

	Seed (95)	Full (4669)	Representative proteomes				NCBI (3985)	Meta (3068)
	Seed (95)	Full (4669)	RP15 (401)	RP35 (765)	RP55 (1004)	RP75 (1160)	NCBI (3985)	Meta (3068)
Alignment:
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

	Seed (95)	Full (4669)	Representative proteomes				NCBI (3985)	Meta (3068)
	Seed (95)	Full (4669)	RP15 (401)	RP35 (765)	RP55 (1004)	RP75 (1160)	NCBI (3985)	Meta (3068)
Raw Stockholm	Download	Download	Download	Download	Download	Download	Download	Download
Gzipped	Download	Download	Download	Download	Download	Download	Download	Download

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

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Curation and family details

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Curation

Seed source:

Pfam-B_1327 (release 4.2)

Previous IDs:

none

Type:

Domain

Author:

Bashton M, Bateman A

Number in seed:

95

Number in full:

4669

Average length of the domain:

257.20 aa

Average identity of full alignment:

42 %

Average coverage of the sequence by the domain:

63.32 %

HMM information

HMM build commands:

build method: hmmbuild -o /dev/null HMM SEED

search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	24.2	24.2
Trusted cut-off	24.2	24.2
Noise cut-off	24.1	24.1

Model length:

261

Family (HMM) version:

15

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Interactive tree

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Interactions

There are 2 interactions for this family. More...

DHQ_synthase Fe-ADH

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the DHQ_synthase domain has been found. There are 45 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

Family: DHQ_synthase (PF01761)

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