Summary: Enoyl-CoA hydratase/isomerase
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This is the Wikipedia entry entitled "Crotonase family". More...
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Crotonase family Edit Wikipedia article
|Enoyl-CoA hydratase/isomerase family|
The crotonase family comprises mechanistically diverse proteins that share a conserved trimeric quaternary structure (sometimes a hexamer consisting of a dimer of trimers), the core of which consists of 4 turns of a (beta/beta/alpha)n superhelix.
Some enzymes in the superfamily have been shown to display dehalogenase, hydratase, and isomerase activities, while others have been implicated in carbon-carbon bond formation and cleavage as well as the hydrolysis of thioesters. However, these different enzymes share the need to stabilize an enolate anion intermediate derived from an acyl-CoA substrate. This is accomplished by two structurally conserved peptidic NH groups that provide hydrogen bonds to the carbonyl moieties of the acyl-CoA substrates and form an "oxyanion hole". The CoA thioester derivatives bind in a characteristic hooked shape and a conserved tunnel binds the pantetheine group of CoA, which links the 3'-phosphate ADP binding site to the site of reaction. Enzymes in the crotonase superfamily include:
- Enoyl-CoA hydratase (crotonase; EC 126.96.36.199), which catalyses the hydratation of 2-trans-enoyl-CoA into 3-hydroxyacyl-CoA.
- 3-2trans-enoyl-CoA isomerase (or dodecenoyl-CoA isomerise; EC 188.8.131.52), which shifts the 3-double bond of the intermediates of unsaturated fatty acid oxidation to the 2-trans position.
- 3-hydroxbutyryl-CoA dehydratase (crotonase; EC 184.108.40.206), a bacterial enzyme involved in the butyrate/butanol-producing pathway.
- 4-Chlorobenzoyl-CoA dehalogenase (EC 220.127.116.11), a Pseudomonas enzyme which catalyses the conversion of 4-chlorobenzoate-CoA to 4-hydroxybenzoate-CoA.
- Dienoyl-CoA isomerase, which catalyses the isomerisation of 3-trans,5-cis-dienoyl-CoA to 2-trans,4-trans-dienoyl-CoA.
- Naphthoate synthase (MenB, or DHNA synthetase; EC 18.104.22.168), a bacterial enzyme involved in the biosynthesis of menaquinone (vitamin K2).
- Carnitine racemase (gene caiD), which catalyses the reversible conversion of crotonobetaine to L-carnitine in Escherichia coli.
- Methylmalonyl CoA decarboxylase (MMCD; EC 22.214.171.124), which has a hexameric structure (dimer of trimers).
- Carboxymethylproline synthase (CarB), which is involved in carbapenem biosynthesis.
- 6-oxo camphor hydrolase, which catalyses the desymmetrization of bicyclic beta-diketones to optically active keto acids.
- The alpha subunit of fatty acid oxidation complex, a multi-enzyme complex that catalyses the last three reactions in the fatty acid beta-oxidation cycle.
- AUH protein, a bifunctional RNA-binding homologue of enoyl-CoA hydratase.
Human proteins containing this domain
- Gerlt JA, Benning MM, Holden HM, Haller T (2001). "The crotonase superfamily: divergently related enzymes that catalyze different reactions involving acyl coenzyme a thioesters". Acc. Chem. Res. 34 (2): 145–57. doi:10.1021/ar000053l. PMID 11263873.
- Brzozowski AM, Leonard PM, Bennett JP, Whittingham JL, Grogan G (2007). "Structural characterization of a beta-diketone hydrolase from the cyanobacterium Anabaena sp. PCC 7120 in native and product-bound forms, a coenzyme A-independent member of the crotonase suprafamily". Biochemistry. 46 (1): 137–44. doi:10.1021/bi061900g. PMID 17198383.
- Wu J, Kisker C, Whitty A, Feng Y, Rudolph MJ, Bell AF, Hofstein HA, Parikh S, Tonge PJ (2002). "Stereoselectivity of enoyl-CoA hydratase results from preferential activation of one of two bound substrate conformers". Chem. Biol. 9 (11): 1247–55. doi:10.1016/S1074-5521(02)00263-6. PMID 12445775.
- Stoffel W, Muller-Newen G (1991). "Mitochondrial 3-2trans-Enoyl-CoA isomerase. Purification, cloning, expression, and mitochondrial import of the key enzyme of unsaturated fatty acid beta-oxidation". Biol. Chem. Hoppe-Seyler. 372 (8): 613–624. doi:10.1515/bchm3.1991.372.2.613. PMID 1958319.
- Dunaway-Mariano D, Benning MM, Wesenberg G, Holden HM, Taylor KL, Yang G, Liu R-Q, Xiang H (1996). "Structure of 4-chlorobenzoyl coenzyme A dehalogenase determined to 1.8 A resolution: an enzyme catalyst generated via adaptive mutation". Biochemistry. 35 (25): 8103–9. doi:10.1021/bi960768p. PMID 8679561.
- Hiltunen JK, Wierenga RK, Modis Y, Filppula SA, Novikov DK, Norledge B (1998). "The crystal structure of dienoyl-CoA isomerase at 1.5 A resolution reveals the importance of aspartate and glutamate sidechains for catalysis". Structure. 6 (8): 957–70. doi:10.1016/s0969-2126(98)00098-7. PMID 9739087.
- Baker EN, Johnston JM, Arcus VL (2005). "Structure of naphthoate synthase (MenB) from Mycobacterium tuberculosis in both native and product-bound forms". Acta Crystallogr. D. 61 (Pt 9): 1199–206. doi:10.1107/S0907444905017531. PMID 16131752.
- Kleber HP, Elssner T, Engemann C, Baumgart K (2001). "Involvement of coenzyme A esters and two new enzymes, an enoyl-CoA hydratase and a CoA-transferase, in the hydration of crotonobetaine to L-carnitine by Escherichia coli". Biochemistry. 40 (37): 11140–8. doi:10.1021/bi0108812. PMID 11551212.
- Gerlt JA, Benning MM, Holden HM, Haller T (2000). "New reactions in the crotonase superfamily: structure of methylmalonyl CoA decarboxylase from Escherichia coli". Biochemistry. 39 (16): 4630–9. doi:10.1021/bi9928896. PMID 10769118.
- Schofield CJ, McDonough MA, Sleeman MC, Sorensen JL, Batchelar ET (2005). "Structural and mechanistic studies on carboxymethylproline synthase (CarB), a unique member of the crotonase superfamily catalyzing the first step in carbapenem biosynthesis". J. Biol. Chem. 280 (41): 34956–65. doi:10.1074/jbc.M507196200. PMID 16096274.
- Leonard PM, Grogan G (2004). "Structure of 6-oxo camphor hydrolase H122A mutant bound to its natural product, (2S,4S)-alpha-campholinic acid: mutant structure suggests an atypical mode of transition state binding for a crotonase homolog". J. Biol. Chem. 279 (30): 31312–17. doi:10.1074/jbc.M403514200. PMID 15138275.
- Resibois-Gregoire A, Dourov N (1966). "Electron microscopic study of a case of cerebral glycogenosis". Acta Neuropathol. 6 (1): 70–9. doi:10.1007/BF00691083. PMID 5229654.
- Nureki O, Fukai S, Yokoyama S, Muto Y, Kurimoto K (2001). "Crystal structure of human AUH protein, a single-stranded RNA binding homolog of enoyl-CoA hydratase". Structure. 9 (12): 1253–63. doi:10.1016/S0969-2126(01)00686-4. PMID 11738050.
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.
Enoyl-CoA hydratase/isomerase Provide feedback
This family contains a diverse set of enzymes including: enoyl-CoA hydratase, napthoate synthase, carnitate racemase, 3-hydroxybutyryl-CoA dehydratase and dodecanoyl-CoA delta-isomerase.
Internal database links
|SCOOP:||Carboxyl_trans CLP_protease ECH_2 MdcE Peptidase_S49 SDH_sah|
|Similarity to PfamA using HHSearch:||ECH_2|
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR001753
The crotonase superfamily is comprised of mechanistically diverse proteins that share a conserved trimeric quaternary structure (sometimes a hexamer consisting of a dimer of trimers), the core of which consists of 4 turns of a (beta/beta/alpha)n superhelix. Some enzymes in the superfamily have been shown to display dehalogenase, hydratase, and isomerase activities, while others have been implicated in carbon-carbon bond formation and cleavage as well as the hydrolysis of thioesters [PUBMED:11263873]. However, these different enzymes share the need to stabilise an enolate anion intermediate derived from an acyl-CoA substrate. This is accomplished by two structurally conserved peptidic NH groups that provide hydrogen bonds to the carbonyl moieties of the acyl-CoA substrates and form an "oxyanion hole". The CoA thioester derivatives bind in a characteristic hooked shape and a conserved tunnel binds the pantetheine group of CoA, which links the 3'-phosphate ADP binding site to the site of reaction [PUBMED:17198383]. Enzymes in the crotonase superfamily include:
- Enoyl-CoA hydratase (crotonase; EC), which catalyses the hydratation of 2-trans-enoyl-CoA into 3-hydroxyacyl-CoA [PUBMED:12445775].
- 3-2trans-enoyl-CoA isomerase (or dodecenoyl-CoA isomerise; EC), which shifts the 3-double bond of the intermediates of unsaturated fatty acid oxidation to the 2-trans position [PUBMED:1958319].
- 3-hydroxbutyryl-CoA dehydratase (crotonase; EC), a bacterial enzyme involved in the butyrate/butanol-producing pathway.
- 4-Chlorobenzoyl-CoA dehalogenase (EC), a Pseudomonas enzyme which catalyses the conversion of 4-chlorobenzoate-CoA to 4-hydroxybenzoate-CoA [PUBMED:8679561].
- Dienoyl-CoA isomerise, which catalyses the isomerisation of 3-trans,5-cis-dienoyl-CoA to 2-trans,4-trans-dienoyl-CoA [PUBMED:9739087].
- Naphthoate synthase (MenB, or DHNA synthetase; EC), a bacterial enzyme involved in the biosynthesis of menaquinone (vitamin K2) [PUBMED:16131752].
- Carnitine racemase (gene caiD), which catalyses the reversible conversion of crotonobetaine to L-carnitine in Escherichia coli [PUBMED:11551212].
- Methylmalonyl CoA decarboxylase (MMCD; EC), which has a hexameric structure (dimer of trimers) [PUBMED:10769118].
- Carboxymethylproline synthase (CarB), which is involved in carbapenem biosynthesis [PUBMED:16096274].
- 6-oxo camphor hydrolase, which catalyses the desymmetrisation of bicyclic beta-diketones to optically active keto acids [PUBMED:15138275].
- The alpha subunit of fatty oxidation complex, a multi-enzyme complex that catalyses the last three reactions in the fatty acid beta-oxidation cycle [PUBMED:5229654].
- AUH protein, a bifunctional RNA-binding homologue of enoyl-CoA hydratase [PUBMED:11738050].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||catalytic activity (GO:0003824)|
|Biological process||metabolic process (GO:0008152)|
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
The graphic that is shown by default represents the longest sequence with a given architecture. Each row contains the following information:
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
- a link to the page in the Pfam site showing information about the sequence that the graphic describes
- the UniProt description of the protein sequence
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Note that you can see the family page for a particular domain by clicking on the graphic. You can also choose to see all sequences which have a given architecture by clicking on the Show link in each row.
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This family includes several peptidases of peptidase clan SK as well as crotonase like proteins.
The clan contains the following 10 members:ACCA Carboxyl_trans CLP_protease ECH_1 ECH_2 MdcE Peptidase_S41 Peptidase_S49 Peptidase_S49_N SDH_sah
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...
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We make a range of alignments for each Pfam-A family:
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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
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.
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This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
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.
|Author:||Finn RD, Eberhardt R|
|Number in seed:||9|
|Number in full:||33223|
|Average length of the domain:||232.20 aa|
|Average identity of full alignment:||24 %|
|Average coverage of the sequence by the domain:||68.61 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 26740544 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||19|
|Download:||download the raw HMM for this family|
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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the More....
This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.
How the sunburst is generated
The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.
In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:
Colouring and labels
Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.
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Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".
Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
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For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.
The tree shows the occurrence of this domain across different species. More...
We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.
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For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.
Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
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There are 6 interactions for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
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 ECH_1 domain has been found. There are 757 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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