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31  structures 700  species 2  interactions 725  sequences 1  architecture

Family: Ecotin (PF03974)

Summary: Ecotin

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This is the Wikipedia entry entitled "Ecotin". More...

Ecotin Edit Wikipedia article

Ecotin
PDB 1ifg EBI.jpg
crystal structure of a monomeric form of general protease inhibitor, ecotin in absence of a protease
Identifiers
Symbol Ecotin
Pfam PF03974
InterPro IPR005658
SCOP 1slu
SUPERFAMILY 1slu

In molecular biology, ecotin is a protease inhibitor which belongs to MEROPS inhibitor family I11, clan IN. Ecotins are dimeric periplasmic proteins from Escherichia coli and related Gram-negative bacteria that have been shown to be potent inhibitors of many trypsin-fold serine proteases of widely varying substrate specificity, which belong to MEROPS peptidase family S1.[1] Phylogenetic analysis suggested that ecotin has an exogenous target, possibly neutrophil elastase. Ecotin from E. coli, Yersinia pestis, and Pseudomonas aeruginosa, all species that encounter the mammalian immune system, inhibit neutrophil elastase strongly while ecotin from the plant pathogen Pantoea citrea inhibits neutrophil elastase 1000-fold less potently.[2] Ecotins all potently inhibit pancreatic digestive peptidases trypsin and chymotrypsin, while showing more variable inhibition of the blood peptidases Factor Xa, thrombin, and urokinase-type plasminogen activator.

External links[edit]

References[edit]

  1. ^ Rawlings ND, Tolle DP, Barrett AJ (March 2004). "Evolutionary families of peptidase inhibitors". Biochem. J. 378 (Pt 3): 705–16. doi:10.1042/BJ20031825. PMC 1224039. PMID 14705960. 
  2. ^ Eggers CT, Murray IA, Delmar VA, Day AG, Craik CS (April 2004). "The periplasmic serine protease inhibitor ecotin protects bacteria against neutrophil elastase". Biochem. J. 379 (Pt 1): 107–18. doi:10.1042/BJ20031790. PMC 1224055. PMID 14705961. 

This article incorporates text from the public domain Pfam and InterPro IPR005658

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.

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Ecotin is a broad range serine protease inhibitor, which forms homodimers. The C-terminal region contains the dimerisation motif [2]. Interestingly, the binding sites show a fluidity of protein contacts binding sites show a fluidity of protein contacts derived from ecotin's innate flexibility in fitting itself to proteases while [4,5].

Literature references

  1. Wang SX, Esmon CT, Fletterick RJ; , Biochemistry 2001;40:10038-10046.: Crystal structure of thrombin-ecotin reveals conformational changes and extended interactions. PUBMED:11513582 EPMC:11513582

  2. Eggers CT, Wang SX, Fletterick RJ, Craik CS; , J Mol Biol 2001;308:975-991.: The role of ecotin dimerization in protease inhibition. PUBMED:11352586 EPMC:11352586

  3. Yang SQ, Wang CI, Gillmor SA, Fletterick RJ, Craik CS; , J Mol Biol 1998;279:945-957.: Ecotin: a serine protease inhibitor with two distinct and interacting binding sites. PUBMED:9642073 EPMC:9642073

  4. McGrath ME, Gillmor SA, Fletterick RJ; , Protein Sci 1995;4:141-148.: Ecotin: lessons on survival in a protease-filled world. PUBMED:7757004 EPMC:7757004

  5. McGrath ME, Erpel T, Bystroff C, Fletterick RJ; , EMBO J 1994;13:1502-1507.: Macromolecular chelation as an improved mechanism of protease inhibition: structure of the ecotin-trypsin complex. PUBMED:8156987 EPMC:8156987


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR023189

Peptide proteinase inhibitors can be found as single domain proteins or as single or multiple domains within proteins; these are referred to as either simple or compound inhibitors, respectively. In many cases they are synthesised as part of a larger precursor protein, either as a prepropeptide or as an N-terminal domain associated with an inactive peptidase or zymogen. This domain prevents access of the substrate to the active site. Removal of the N-terminal inhibitor domain either by interaction with a second peptidase or by autocatalytic cleavage activates the zymogen. Other inhibitors interact direct with proteinases using a simple noncovalent lock and key mechanism; while yet others use a conformational change-based trapping mechanism that depends on their structural and thermodynamic properties.

This entry represents proteinase inhibitors that belong to MEROPS inhibitor family I11, clan IN. Ecotins are dimeric periplasmic proteins from Escherichia coli and related Gram-negative bacteria that have been shown to be potent inhibitors of many trypsin-fold serine proteases of widely varying substrate specificity, which belong to MEROPS peptidase family S1 (INTERPRO) [PUBMED:14705960]. Phylogenetic analysis suggested that ecotin has an exogenous target, possibly neutrophil elastase. Ecotin from E. coli, Yersinia pestis, and Pseudomonas aeruginosa, all species that encounter the mammalian immune system inhibit neutrophil elastase strongly while ecotin from the plant pathogen Pantoea citrea inhibits neutrophil elastase 1000-fold less than the others [PUBMED:14705961].

They all potently inhibit pancreatic digestive peptidases trypsin and chymotrypsin, while showing more variable inhibition of the blood peptidases Factor Xa, thrombin, and urokinase-type plasminogen activator.

This entry represents the structural domain of ecotin, consisting of 8 beta strands organised in 2 sheets.

Domain organisation

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

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Alignments

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(47)
Full
(725)
Representative proteomes NCBI
(328)
Meta
(19)
RP15
(13)
RP35
(29)
RP55
(57)
RP75
(89)
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  Seed
(47)
Full
(725)
Representative proteomes NCBI
(328)
Meta
(19)
RP15
(13)
RP35
(29)
RP55
(57)
RP75
(89)
Alignment:
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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
(47)
Full
(725)
Representative proteomes NCBI
(328)
Meta
(19)
RP15
(13)
RP35
(29)
RP55
(57)
RP75
(89)
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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.

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HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

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.

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.

Curation View help on the curation process

Seed source: Pfam-B_54504 (release 7.2)
Previous IDs: none
Type: Family
Author: Finn RD
Number in seed: 47
Number in full: 725
Average length of the domain: 124.20 aa
Average identity of full alignment: 65 %
Average coverage of the sequence by the domain: 76.27 %

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 22.2 22.2
Trusted cut-off 24.0 24.2
Noise cut-off 21.7 21.2
Model length: 128
Family (HMM) version: 8
Download: download the raw HMM for this family

Species distribution

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Interactions

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

Trypsin Ecotin

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 Ecotin domain has been found. There are 31 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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