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502  structures 4081  species 2  interactions 26211  sequences 113  architectures

Family: ECH (PF00378)

Summary: Enoyl-CoA hydratase/isomerase family

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Crotonase family". More...

Crotonase family Edit Wikipedia article

Enoyl-CoA hydratase/isomerase family
Identifiers
Symbol ECH
Pfam PF00378
InterPro IPR001753
PROSITE PDOC00150
SCOP 1dub
SUPERFAMILY 1dub
CDD cd06558

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.[1] 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.[2] Enzymes in the crotonase superfamily include:

Human proteins containing this domain[edit]

AUH; CDY2B; CDYL; CDYL2; DCI; ECH1; ECHDC1; ECHDC2; ECHDC3; ECHS1; EHHADH; HADHA; HCA64; HIBCH; PECI;

References[edit]

  1. ^ 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. PMID 11263873. 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ 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. 
  5. ^ 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. 
  6. ^ 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. PMID 9739087. 
  7. ^ 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. 
  8. ^ 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. 
  9. ^ 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. 
  10. ^ 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. 
  11. ^ 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. 
  12. ^ 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. 
  13. ^ 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 article incorporates text from the public domain Pfam and InterPro IPR001753

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.

Enoyl-CoA hydratase/isomerase family Provide feedback

This family contains a diverse set of enzymes including: Enoyl-CoA hydratase (Q13011). Napthoate synthase (P27290). Carnitate racemase (P31551). 3-hydoxybutyryl-CoA dehydratase (P52046). Dodecanoyl-CoA delta-isomerase (P42126).

Internal database links

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].

This entry represents the core domain found in crotonase superfamily members.

Gene Ontology

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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 ClpP_crotonase (CL0127), which has the following description:

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 ECH_C MdcE Peptidase_S41 Peptidase_S49 Peptidase_S49_N SDH_sah

Alignments

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  Seed
(13)
Full
(26211)
Representative proteomes NCBI
(22457)
Meta
(13530)
RP15
(2394)
RP35
(5222)
RP55
(7277)
RP75
(8836)
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  Seed
(13)
Full
(26211)
Representative proteomes NCBI
(22457)
Meta
(13530)
RP15
(2394)
RP35
(5222)
RP55
(7277)
RP75
(8836)
Alignment:
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  Seed
(13)
Full
(26211)
Representative proteomes NCBI
(22457)
Meta
(13530)
RP15
(2394)
RP35
(5222)
RP55
(7277)
RP75
(8836)
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

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

HMM logo

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Trees

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.

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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: Prosite
Previous IDs: none
Type: Family
Author: Finn RD
Number in seed: 13
Number in full: 26211
Average length of the domain: 233.90 aa
Average identity of full alignment: 23 %
Average coverage of the sequence by the domain: 67.75 %

HMM information View help on HMM parameters

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 21.7 21.7
Trusted cut-off 21.7 21.7
Noise cut-off 21.6 21.6
Model length: 245
Family (HMM) version: 15
Download: download the raw HMM for this family

Species distribution

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Interactions

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

Thiolase_N ECH

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 ECH domain has been found. There are 502 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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