EzCatDB: M00227
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DB codeM00227
RLCP classification1.13.30000.10 : Hydrolysis
CATH domainDomain 1-.-.-.-
Domain 23.30.70.960 : Alpha-Beta Plaits
Domain 32.60.120.290 : Jelly Rolls
Domain 42.-.-.-
Domain 52.60.120.290 : Jelly Rolls
Domain 6-.-.-.-
Domain 73.10.250.10 : Mac-2 Binding Protein
Domain 82.40.10.10 : Thrombin, subunit HCatalytic domain
Domain 92.40.10.10 : Thrombin, subunit HCatalytic domain
E.C.3.4.21.9

CATH domainRelated DB codes (homologues)
2.40.10.10 : Thrombin, subunit HM00139,D00214,M00167,D00426,M00133,D00428,D00429,D00430,D00431,D00432,D00433,D00434,D00435,M00209,D00194,D00197,D00211,D00212,D00216,M00212,D00224,D00497,M00217,M00216,D00528,D00848,D00850,D00851,D00852,D00855,M00152,M00155,M00157,M00181,M00315,M00316,M00317,M00348,M00349,T00074,T00410,T00411
2.60.120.290 : Jelly RollsM00139,M00315,M00316,M00317,M00348
3.10.250.10 : Mac-2 Binding ProteinM00349
3.30.70.960 : Alpha-Beta PlaitsM00348

Enzyme Name
UniProtKBKEGG

P98072
Protein nameEnteropeptidaseenteropeptidase
enterokinase
SynonymsEC 3.4.21.9
Enterokinase
Serine protease 7
ContainsEnteropeptidase non-catalytic heavy chain
Enteropeptidase catalytic light chain
RefSeqNP_776864.1 (Protein)
NM_174439.2 (DNA/RNA sequence)
MEROPSS01.156 (Serine)
PfamPF00431 (CUB)
PF00057 (Ldl_recept_a)
PF00629 (MAM)
PF01390 (SEA)
PF00530 (SRCR)
PF00089 (Trypsin)
[Graphical view]


UniProtKB:Accession NumberP98072
Entry nameENTK_BOVIN
ActivityActivation of trypsinogen by selective cleavage of 6-Lys-|-Ile-7 bond.
SubunitHeterodimer of a catalytic (light) chain and a multidomain (heavy) chain linked by a disulfide bond.
Subcellular locationMembrane, Single-pass type II membrane protein (Probable).
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idL00076C00001C00298I00087I00085I00086
CompoundTrypsinogenH2OTrypsinPeptidyl-tetrahedral intermediateAcyl-enzymeTetrahedral intermediate
Typepeptide/proteinH2Opeptide/protein


ChEBI
15377




PubChem
962
22247451




              
1ekbB01Unbound UnboundUnboundUnboundIntermediate-analogue:ASP-ASP-ASP-LYS(chain C)
1ekbB02Unbound UnboundUnboundUnboundUnbound

Active-site residues
pdbCatalytic residuesMain-chain involved in catalysis
          
1ekbB01SER 195
GLY 193;ASP 194;SER 195(mainchain amide)
1ekbB02HIS 57;ASP 102
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[10]p.364

references
[1]
PubMed ID12810
JournalBiochim Biophys Acta
Year1976
Volume452
Pages488-96
AuthorsBaratti J, Maroux S
TitleOn the catalytic and binding sites of porcine enteropeptidase.
[2]
PubMed ID8051081
JournalJ Biol Chem
Year1994
Volume269
Pages19976-82
AuthorsMatsushima M, Ichinose M, Yahagi N, Kakei N, Tsukada S, Miki K, Kurokawa K, Tashiro K, Shiokawa K, Shinomiya K, et al
TitleStructural characterization of porcine enteropeptidase.
[3]
PubMed ID8052624
JournalProc Natl Acad Sci U S A
Year1994
Volume91
Pages7588-92
AuthorsKitamoto Y, Yuan X, Wu Q, McCourt DW, Sadler JE
TitleEnterokinase, the initiator of intestinal digestion, is a mosaic protease composed of a distinctive assortment of domains.
[4]
PubMed ID8962677
JournalBiol Chem Hoppe Seyler
Year1995
Volume376
Pages681-4
AuthorsWang ZM, Rubin H, Schechter NM
TitleProduction of active recombinant human chymase from a construct containing the enterokinase cleavage site of trypsinogen in place of the native propeptide sequence.
[5]
PubMed ID9636275
JournalBiotechnology (N Y)
Year1995
Volume13
Pages982-7
AuthorsCollins-Racie LA, McColgan JM, Grant KL, DiBlasio-Smith EA, McCoy JM, LaVallie ER
TitleProduction of recombinant bovine enterokinase catalytic subunit in Escherichia coli using the novel secretory fusion partner DsbA.
[6]
PubMed ID9636316
JournalBiotechnology (N Y)
Year1996
Volume14
Pages77-81
AuthorsVozza LA, Wittwer L, Higgins DR, Purcell TJ, Bergseid M, Collins-Racie LA, LaVallie ER, Hoeffler JP
TitleProduction of a recombinant bovine enterokinase catalytic subunit in the methylotrophic yeast Pichia pastoris.
[7]
PubMed ID9395456
JournalJ Biol Chem
Year1997
Volume272
Pages31293-300
AuthorsLu D, Yuan X, Zheng X, Sadler JE
TitleBovine proenteropeptidase is activated by trypsin, and the specificity of enteropeptidase depends on the heavy chain.
[8]
PubMed ID10094769
JournalAnal Biochem
Year1999
Volume269
Pages10-6
AuthorsHosfield T, Lu Q
TitleInfluence of the amino acid residue downstream of (Asp)4Lys on enterokinase cleavage of a fusion protein.
[9]
PubMed ID9880538
JournalJ Biol Chem
Year1999
Volume274
Pages1596-605
AuthorsZheng X, Lu D, Sadler JE
TitleApical sorting of bovine enteropeptidase does not involve detergent-resistant association with sphingolipid-cholesterol rafts.
[10]
CommentsX-ray crystallography
PubMed ID10493881
JournalJ Mol Biol
Year1999
Volume292
Pages361-73
AuthorsLu D, Futterer K, Korolev S, Zheng X, Tan K, Waksman G, Sadler JE
TitleCrystal structure of enteropeptidase light chain complexed with an analog of the trypsinogen activation peptide.
Related PDB1ekb
[11]
PubMed ID10656339
JournalJ Biotechnol
Year2000
Volume76
Pages245-51
AuthorsSvetina M, Krasevec N, Gaberc-Porekar V, Komel R
TitleExpression of catalytic subunit of bovine enterokinase in the filamentous fungus Aspergillus niger.
[12]
PubMed ID11719902
JournalAm J Hum Genet
Year2002
Volume70
Pages20-5
AuthorsHolzinger A, Maier EM, Buck C, Mayerhofer PU, Kappler M, Haworth JC, Moroz SP, Hadorn HB, Sadler JE, Roscher AA
TitleMutations in the proenteropeptidase gene are the molecular cause of congenital enteropeptidase deficiency.
[13]
PubMed ID11913964
JournalArch Biochem Biophys
Year2002
Volume400
Pages1-6
AuthorsSong HW, Choi SI, Seong BL
TitleEngineered recombinant enteropeptidase catalytic subunit: effect of N-terminal modification.

comments
This enzyme belongs to the peptidase family-S1.
This protein is composed of a non-catalytic heavy chain, which is a multidomain bound to membrane, and a catalytic light chain. These two chains are linked by a disulfide bond (see [3]). The tertiary strucutre of the catalytic chain has been determined so far. (The chain A in 1ekb is a C-terminal fragment of heavy chain.) However, the homologous domains have been elucidated. Moreover, this enzyme is a member of type II transmembrane serine protease family (see M00348, M00349 in EzCatDB).
According to the literature [10], this enzyme has got the catalytic triad, which is a signature of serine proteases; His57, Asp102 and Ser195. Moreover, the Ser195 is bound to the C-terminal of Lys residue, to form a tetrahedral hemiketal intermediate, which showed that Ser195 could function as nucleophile.

createdupdated
2004-03-262012-08-06


Copyright: Nozomi Nagano, JST & CBRC-AIST
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Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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