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64  structures 6879  species 0  interactions 12923  sequences 139  architectures

Family: Shikimate_DH (PF01488)

Summary: Shikimate / quinate 5-dehydrogenase

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This is the Wikipedia entry entitled "Shikimate dehydrogenase". More...

Shikimate dehydrogenase Edit Wikipedia article

Shikimate dehydrogenase
Shikimate Dehydrogenase Cartoon 1.png
EC no.
CAS no.9026-87-3
IntEnzIntEnz view
ExPASyNiceZyme view
MetaCycmetabolic pathway
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO

In enzymology, a shikimate dehydrogenase (EC is an enzyme that catalyzes the chemical reaction

shikimate + NADP+ 3-dehydroshikimate + NADPH + H+

Thus, the two substrates of this enzyme are shikimate and NADP+, whereas its 3 products are 3-dehydroshikimate, NADPH, and H+. This enzyme participates in phenylalanine, tyrosine and tryptophan biosynthesis.


Shikimate dehydrogenase is an enzyme that catalyzes one step of the shikimate pathway. This pathway is found in bacteria, plants, fungi, algae, and parasites and is responsible for the biosynthesis of aromatic amino acids (phenylalanine, tyrosine, and tryptophan) from the metabolism of carbohydrates. In contrast, animals and humans lack this pathway hence products of this biosynthetic route are essential amino acids that must be obtained through an animal's diet.

There are seven enzymes that play a role in this pathway. Shikimate dehydrogenase (also known as 3-dehydroshikimate dehydrogenase) is the fourth step of the seven step process. This step converts 3-dehydroshikimate to shikimate as well as reduces NADP+ to NADPH.


This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is shikimate:NADP+ 3-oxidoreductase. Other names in common use include:

  • dehydroshikimic reductase,
  • shikimate oxidoreductase,
  • shikimate:NADP+ oxidoreductase,
  • 5-dehydroshikimate reductase,
  • shikimate 5-dehydrogenase,
  • 5-dehydroshikimic reductase,
  • DHS reductase,
  • shikimate:NADP+ 5-oxidoreductase, and
  • AroE.


The Shikimate Dehydrogenase Reaction

Shikimate Dehydrogenase catalyzes the reversible NADPH-dependent reaction of 3-dehydroshikimate to shikimate.[1] The enzyme reduces the carbon-oxygen double bond of a carbonyl functional group to a hydroxyl (OH) group, producing the shikimate anion. The reaction is NADPH dependent with NADPH being oxidised to NADP+.


N terminal domain

Shikimate dehydrogenase, N terminal domain
PDB 1nyt EBI.jpg
Shikimate dehydrogenase AroE complexed with NADP+

The Shikimate dehydrogenase substrate binding domain found at the N-terminus binds to the substrate, 3-dehydroshikimate.[2] It is considered to be the catalytic domain. It has a structure of six beta strands forming a twisted beta sheet with four alpha helices.[2]

C terminal domain

Shikimate Dehydrogenase C terminal
PDB 1gpj EBI.jpg
Glutamyl-tRNA reductase from methanopyrus kandleri
Pfam clanCL0063

The C-terminal domain binds to NADPH. It has a special structure, a Rossmann fold, whereby six-stranded twisted and parallel beta sheet with loops and alpha helices surrounding the core beta sheet.[2]

The Structure of Shikimate dehydrogenase is characterized by two domains, two alpha helices and two beta sheets with a large cleft separating the domains of the monomer.[3] The enzyme is symmetrical. Shikimate dehydrogenase also has an NADPH binding site that contains a Rossmann fold. This binding site normally contains a glycine P-loop.[1] The domains of the monomer show a fair amount of flexibility suggesting that the enzyme can open in close to bind with the substrate 3-Dehydroshikimate. Hydrophobic interactions occur between the domains and the NADPH binding site.[1] This hydrophobic core and its interactions lock the shape of the enzyme even though the enzyme is a dynamic structure. There is also evidence to support that the structure of the enzyme is conserved, meaning the structure takes sharp turns in order to take up less space.

The cleft in the shikimate dehydrogenase monomer. The green selection is the loops surrounding the cleft, and the red selection shows alpha helices in the background.


Escherichia coli (E. coli) expresses two different forms of shikimate dehydrogenase, AroE and YdiB. These two forms are paralogs of each other. The two forms of shikimate dehydrogenase have different primary sequences in different organisms but catalyze the same reactions. There is about 25% similarity between the sequences of AroE and YdiB, but their two structures have similar structures with similar folds. YdiB can utilize NAD or NADP as a cofactor and also reacts with quinic acid.[3] They both have high affinity of their ligands as shown by their similar enzyme (Km) values.[3] Both forms of the enzyme are independently regulated.[3]

Shikimate dehydrogenase YdiB with highlighted NADH binding sites. The red color of the surface of the structure shows alpha helices, the yellow shows beta sheets, and the green area shows where there are loops in the enzyme.
The AroE form of shikimate dehydrogenase with highlighted NADP+ binding sites. The red color shows where the alpha helices are, the green shows the loops, and the yellow shows the beta sheets in the structure.


The shikimate pathway is a target for herbicides and other non-toxic drugs because the shikimate pathway is not present in humans. Glyphosate, a commonly used herbicide, is an inhibitor of 5-enolpyruvylshikimate 3-phosphate synthase or EPSP synthase, an enzyme in the shikimate pathway. The problem is that this herbicide has been utilized for about 20 years and now some plants have now emerged that are glyphosate-resistant. This has relevance to research on shikimate dehydrogenase because it is important to maintain diversity in the enzyme blocking process in the shikimate pathway and with more research shikimate dehydrogenase could be the next enzyme to be inhibited in the shikimate pathway. In order to design new inhibitors the structures for all the enzymes in the pathway have needed to be elucidated. The presence of two forms of the enzyme complicate the design of potential drugs because one could compensate for the inhibition of the other. Also there the TIGR data base shows that there are 14 species of bacteria with the two forms of shikimate dehydrogenase.[3] This is a problem for drug makers because there are two enzymes that a potential drug would need to inhibit at the same time.[3]


  1. ^ a b c Ye S, Von Delft F, Brooun A, Knuth MW, Swanson RV, McRee DE (July 2003). "The crystal structure of shikimate dehydrogenase (AroE) reveals a unique NADPH binding mode". J. Bacteriol. 185 (14): 4144–51. doi:10.1128/JB.185.14.4144-4151.2003. PMC 164887. PMID 12837789.
  2. ^ a b c Lee HH (2012). "High-resolution structure of shikimate dehydrogenase from Thermotoga maritima reveals a tightly closed conformation". Mol Cells. 33 (3): 229–33. doi:10.1007/s10059-012-2200-x. PMC 3887703. PMID 22095087.
  3. ^ a b c d e f Michel G, Roszak AW, Sauvé V, Maclean J, Matte A, Coggins JR, Cygler M, Lapthorn AJ (May 2003). "Structures of shikimate dehydrogenase AroE and its Paralog YdiB. A common structural framework for different activities". J. Biol. Chem. 278 (21): 19463–72. doi:10.1074/jbc.M300794200. PMID 12637497.

Further reading

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Shikimate / quinate 5-dehydrogenase Provide feedback

This family contains both shikimate and quinate dehydrogenases. Shikimate 5-dehydrogenase catalyses the conversion of shikimate to 5-dehydroshikimate. This reaction is part of the shikimate pathway which is involved in the biosynthesis of aromatic amino acids. Quinate 5-dehydrogenase catalyses the conversion of quinate to 5-dehydroquinate. This reaction is part of the quinate pathway where quinic acid is exploited as a source of carbon in prokaryotes and microbial eukaryotes. Both the shikimate and quinate pathways share two common pathway metabolites 3-dehydroquinate and dehydroshikimate.

Literature references

  1. Hawkins AR, Lamb HK; , Eur J Biochem 1995;232:7-18.: The molecular biology of multidomain proteins. Selected examples. PUBMED:7556173 EPMC:7556173

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR006151

This entry represents a domain found in shikimate and quinate dehydrogenases, as well as glutamyl-tRNA reductases.

Shikimate 5-dehydrogenase ( EC ) catalyses the conversion of shikimate to 5-dehydroshikimate [ PUBMED:12906831 , PUBMED:12837789 ]. This reaction is part of the shikimate pathway which is involved in the biosynthesis of aromatic amino acids [ PUBMED:15012217 ]. Quinate 5-dehydrogenase catalyses the conversion of quinate to 5-dehydroquinate. This reaction is part of the quinate pathway where quinic acid is exploited as a source of carbon in prokaryotes and microbial eukaryotes. Both the shikimate and quinate pathways share two common pathway metabolites, 3-dehydroquinate and dehydroshikimate.

Glutamyl-tRNA reductase ( EC ) catalyzes the first step of tetrapyrrole biosynthesis in plants, archaea and most bacteria. The dimeric enzyme has an unusual V-shaped architecture where each monomer consists of three domains linked by a long 'spinal' alpha-helix. The central catalytic domain specifically recognises the glutamate moiety of the substrate [ PUBMED:16228559 ].

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 NADP_Rossmann (CL0063), which has the following description:

A class of redox enzymes are two domain proteins. One domain, termed the catalytic domain, confers substrate specificity and the precise reaction of the enzyme. The other domain, which is common to this class of redox enzymes, is a Rossmann-fold domain. The Rossmann domain binds nicotinamide adenine dinucleotide (NAD+) and it is this cofactor that reversibly accepts a hydride ion, which is lost or gained by the substrate in the redox reaction. Rossmann domains have an alpha/beta fold, which has a central beta sheet, with approximately five alpha helices found surrounding the beta sheet.The strands forming the beta sheet are found in the following characteristic order 654123. The inter sheet crossover of the stands in the sheet form the NAD+ binding site [1]. In some more distantly relate Rossmann domains the NAD+ cofactor is replaced by the functionally similar cofactor FAD.

The clan contains the following 209 members:

2-Hacid_dh_C 3Beta_HSD 3HCDH_N 3HCDH_RFF adh_short adh_short_C2 ADH_zinc_N ADH_zinc_N_2 AdoHcyase_NAD AdoMet_MTase AlaDh_PNT_C Amino_oxidase ApbA AviRa B12-binding Bac_GDH Bin3 Bmt2 BMT5-like BpsA_C CARME CbiJ CheR CMAS CmcI CoA_binding CoA_binding_2 CoA_binding_3 Cons_hypoth95 CoV_ExoN CoV_Methyltr_2 DAO DapB_N DFP DNA_methylase DOT1 DRE2_N DREV DUF1442 DUF1611_N DUF166 DUF1776 DUF268 DUF2855 DUF3410 DUF364 DUF5129 DUF5130 DUF6094 DUF938 DXP_reductoisom DXPR_C Eco57I ELFV_dehydrog Eno-Rase_FAD_bd Eno-Rase_NADH_b Enoyl_reductase Epimerase F420_oxidored FAD_binding_2 FAD_binding_3 FAD_oxidored Fibrillarin FMO-like FmrO FtsJ fvmX7 G6PD_N GCD14 GDI GDP_Man_Dehyd GFO_IDH_MocA GIDA GidB GLF Glu_dehyd_C Glyco_hydro_4 Glyco_tran_WecG GMC_oxred_N Gp_dh_N GRAS GRDA HcgC HI0933_like HIM1 IlvN ISPD_C KR LCM Ldh_1_N LpxI_N Lycopene_cycl Lys_Orn_oxgnase Malic_M Mannitol_dh MCRA Met_10 Methyltr_RsmB-F Methyltr_RsmF_N Methyltrans_Mon Methyltrans_SAM Methyltransf_10 Methyltransf_11 Methyltransf_12 Methyltransf_14 Methyltransf_15 Methyltransf_16 Methyltransf_17 Methyltransf_18 Methyltransf_19 Methyltransf_2 Methyltransf_20 Methyltransf_21 Methyltransf_22 Methyltransf_23 Methyltransf_24 Methyltransf_25 Methyltransf_28 Methyltransf_29 Methyltransf_3 Methyltransf_30 Methyltransf_31 Methyltransf_32 Methyltransf_33 Methyltransf_34 Methyltransf_4 Methyltransf_5 Methyltransf_7 Methyltransf_8 Methyltransf_9 Methyltransf_PK MethyltransfD12 MetW Mg-por_mtran_C MmeI_Mtase MOLO1 Mqo MT-A70 MTS Mur_ligase N6-adenineMlase N6_Mtase N6_N4_Mtase NAD_binding_10 NAD_binding_2 NAD_binding_3 NAD_binding_4 NAD_binding_5 NAD_binding_7 NAD_binding_8 NAD_binding_9 NAD_Gly3P_dh_N NAS NmrA NNMT_PNMT_TEMT NodS OCD_Mu_crystall OpcA_G6PD_assem Orbi_VP4 PALP PARP_regulatory PCMT PDH_N PglD_N Polysacc_syn_2C Polysacc_synt_2 Pox_MCEL Pox_mRNA-cap Prenylcys_lyase PrmA PRMT5 Pyr_redox Pyr_redox_2 Pyr_redox_3 Reovirus_L2 RmlD_sub_bind Rossmann-like rRNA_methylase RrnaAD Rsm22 RsmJ Sacchrp_dh_NADP SAM_MT SE Semialdhyde_dh Shikimate_DH Spermine_synth SRR1 TehB THF_DHG_CYH_C Thi4 ThiF TPM_phosphatase TPMT TrkA_N TRM TRM13 TrmK tRNA_U5-meth_tr Trp_halogenase TylF Ubie_methyltran UDPG_MGDP_dh_N UPF0020 UPF0146 Urocanase V_cholerae_RfbT XdhC_C YjeF_N


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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Pfam-B_336 (release 4.0)
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Bashton M , Bateman A
Number in seed: 35
Number in full: 12923
Average length of the domain: 112.80 aa
Average identity of full alignment: 24 %
Average coverage of the sequence by the domain: 25.96 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 24.3 24.3
Trusted cut-off 24.3 24.3
Noise cut-off 24.2 24.2
Model length: 138
Family (HMM) version: 23
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Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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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 Shikimate_DH domain has been found. There are 64 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 sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A0P0V319 View 3D Structure Click here
A0A0R0LCZ4 View 3D Structure Click here
A0A1D6GNK4 View 3D Structure Click here
A0A1D6IWN4 View 3D Structure Click here
A0B577 View 3D Structure Click here
A0B999 View 3D Structure Click here
A0JYN2 View 3D Structure Click here
A0KEX8 View 3D Structure Click here
A0KMZ9 View 3D Structure Click here
A0L3K8 View 3D Structure Click here
A0LDT6 View 3D Structure Click here
A0LIM5 View 3D Structure Click here
A0LLU7 View 3D Structure Click here
A0LRF2 View 3D Structure Click here
A0Q2B3 View 3D Structure Click here
A0QR17 View 3D Structure Click here
A0RXF8 View 3D Structure Click here
A1AUE9 View 3D Structure Click here
A1AW87 View 3D Structure Click here
A1AX01 View 3D Structure Click here
A1B5V3 View 3D Structure Click here
A1BHD5 View 3D Structure Click here
A1K3B9 View 3D Structure Click here
A1K442 View 3D Structure Click here
A1R8A6 View 3D Structure Click here
A1S1K8 View 3D Structure Click here
A1S8R3 View 3D Structure Click here
A1SE01 View 3D Structure Click here
A1SI37 View 3D Structure Click here
A1SR30 View 3D Structure Click here
A1SV88 View 3D Structure Click here
A1T3D2 View 3D Structure Click here
A1TKF1 View 3D Structure Click here
A1TTC3 View 3D Structure Click here
A1UAP7 View 3D Structure Click here
A1UQU2 View 3D Structure Click here
A1VKB7 View 3D Structure Click here
A1W4B9 View 3D Structure Click here
A1WBZ2 View 3D Structure Click here
A1WI55 View 3D Structure Click here