EzCatDB: S00347

DB codeS00347
RLCP classification1.12.30000.10
CATH domainDomain 13.40.50.1820Catalytic domain
E.C.3.1.1.3,3.1.1.13
CSA1aql

CATH domainRelated DB codes (homologues)
3.40.50.1820S00544,S00344,S00517,S00525,S00526,S00720,S00723,S00724,S00725,S00919,S00057,S00374,S00345,S00348,S00346,S00350,S00352,S00353,S00355,S00356,S00358,D00189,D00210,D00539,T00253

Enzyme Name
Swiss-protKEGG

P30122P19835
Protein nameBile salt-activated lipaseBile salt-activated lipasetriacylglycerol lipase
   (EC 3.1.1.3)

lipase
   (EC 3.1.1.3)

triglyceride lipase
   (EC 3.1.1.3)

tributyrase
   (EC 3.1.1.3)

butyrinase
   (EC 3.1.1.3)

glycerol ester hydrolase
   (EC 3.1.1.3)

tributyrinase
   (EC 3.1.1.3)

Tween hydrolase
   (EC 3.1.1.3)

steapsin
   (EC 3.1.1.3)

triacetinase
   (EC 3.1.1.3)

tributyrin esterase
   (EC 3.1.1.3)

Tweenase
   (EC 3.1.1.3)

amno N-AP
   (EC 3.1.1.3)

Takedo 1969-4-9
   (EC 3.1.1.3)

Meito MY 30
   (EC 3.1.1.3)

Tweenesterase
   (EC 3.1.1.3)

GA 56
   (EC 3.1.1.3)

capalase L
   (EC 3.1.1.3)

triglyceride hydrolase
   (EC 3.1.1.3)

triolein hydrolase
   (EC 3.1.1.3)

tween-hydrolyzing esterase
   (EC 3.1.1.3)

amano CE
   (EC 3.1.1.3)

cacordase
   (EC 3.1.1.3)

triglyceridase
   (EC 3.1.1.3)

triacylglycerol ester hydrolase
   (EC 3.1.1.3)

amano P
   (EC 3.1.1.3)

amano AP
   (EC 3.1.1.3)

PPL
   (EC 3.1.1.3)

glycerol-ester hydrolase
   (EC 3.1.1.3)

GEH
   (EC 3.1.1.3)

meito Sangyo OF lipase
   (EC 3.1.1.3)

hepatic lipase
   (EC 3.1.1.3)

lipazin
   (EC 3.1.1.3)

post-heparin plasma protamine-resistant lipase
   (EC 3.1.1.3)

salt-resistant post-heparin lipase
   (EC 3.1.1.3)

heparin releasable hepatic lipase
   (EC 3.1.1.3)

amano CES
   (EC 3.1.1.3)

amano B
   (EC 3.1.1.3)

tributyrase
   (EC 3.1.1.3)

triglyceride lipase
   (EC 3.1.1.3)

liver lipase
   (EC 3.1.1.3)

hepatic monoacylglycerol acyltransferase
   (EC 3.1.1.3)

sterol esterase
   (EC 3.1.1.13)

cholesterol esterase
   (EC 3.1.1.13)

cholesteryl ester synthase
   (EC 3.1.1.13)

triterpenol esterase
   (EC 3.1.1.13)

cholesteryl esterase
   (EC 3.1.1.13)

cholesteryl ester hydrolase
   (EC 3.1.1.13)

sterol ester hydrolase
   (EC 3.1.1.13)

cholesterol ester hydrolase
   (EC 3.1.1.13)

cholesterase
   (EC 3.1.1.13)

acylcholesterol lipase
   (EC 3.1.1.13)

SynonymsBAL
EC 3.1.1.3
EC 3.1.1.13
Bile salt-stimulated lipase
BSSL
Carboxyl ester lipase
Sterol esterase
Cholesterol esterase
Pancreatic lysophospholipase
BAL
EC 3.1.1.3
EC 3.1.1.13
Bile salt-stimulated lipase
BSSL
Carboxyl ester lipase
Sterol esterase
Cholesterol esterase
Pancreatic lysophospholipase
Bucelipase

KEGG pathways
MAP codePathwaysE.C.
MAP00120Bile acid biosynthesis3.1.1.13
MAP00561Glycerolipid metabolism3.1.1.3

Swiss-prot:Accession NumberP30122P19835
Entry nameCEL_BOVINCEL_HUMAN
ActivityTriacylglycerol + H(2)O = diacylglycerol + a carboxylate.,A steryl ester + H(2)O = a sterol + a fatty acid.Triacylglycerol + H(2)O = diacylglycerol + a carboxylate.,A steryl ester + H(2)O = a sterol + a fatty acid.
Subunit

Subcellular location

Cofactor



SubstratesProductsintermediates
KEGG-idC00422C01958C00001C00165C00370C00060C00162I00123I00085I00086
E.C.3.1.1.33.1.1.133.1.1.3,3.1.1.133.1.1.33.1.1.133.1.1.33.1.1.133.1.1.3,3.1.1.133.1.1.3,3.1.1.133.1.1.3,3.1.1.13
CompoundTriacylglycerolSteryl esterH2ODiacylglycerolSterolCarboxylateFatty acidPeptidyl-Ser-tetrahedral intermediate (with previous carboxylic-ester)Acyl-enzyme(Peptidyl-Ser-acyl group)Peptidyl-Ser-tetrahedral-intermediate
Typecarbohydrate,lipidcarbohydrate,steroidH2Ocarbohydrate,lipidcarbohydrate,steroidcarboxyl groupfatty acid


1aqlAUnboundUnbound
UnboundAnalogue:2xTCHUnboundUnboundUnboundUnboundUnbound
1aqlBUnboundUnbound
UnboundAnalogue:2xTCHUnboundUnboundUnboundUnboundUnbound
2bceAUnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1aknAUnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1f6wAUnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1jmyAUnboundUnbound
UnboundUnboundUnboundUnboundUnboundUnboundUnbound

Active-site residues
pdbCatalytic residuesMain-chain involved in catalysis
1aqlASER 194;ASP 320;HIS 435
GLY 107;ALA 195
1aqlBSER 194;ASP 320;HIS 435
GLY 107;ALA 195
2bceASER 194;ASP 320;HIS 435
GLY 107;ALA 195
1aknASER 194;ASP 320;HIS 435
GLY 107;ALA 195
1f6wASER 194;ASP 320;HIS 435
GLY 107;ALA 195
1jmyASER 194;ASP 320;HIS 435
GLY 107;ALA 195

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[2]p.5116, Fig.94
[4]Fig.5
[5]Fig.1
[7]Fig.4
[8]p.1787

references
[1]
CommentsX-ray crystallography (2.8 Angstroms)
PubMed ID9331420
JournalStructure
Year1997
Volume5
Pages1209-18
AuthorsWang X, Wang CS, Tang J, Dyda F, Zhang XC
TitleThe crystal structure of bovine bile salt activated lipase: insights into the bile salt activation mechanism.
Related PDB1aql,1akn
[2]
CommentsX-ray crystallography (1.6 Angstroms), catalysis
PubMed ID9548741
JournalBiochemistry
Year1998
Volume37
Pages5107-17
AuthorsChen JC, Miercke LJ, Krucinski J, Starr JR, Saenz G, Wang X, Spilburg CA, Lange LG, Ellsworth JL, Stroud RM
TitleStructure of bovine pancreatic cholesterol esterase at 1.6 A: novel structural features involved in lipase activation.
Related PDB2bce
[3]
Commentscatalysis (inhibitor)
PubMed ID9774723
JournalBiochim Biophys Acta
Year1998
Volume1388
Pages161-74
AuthorsLin G, Tsai YC, Liu HC, Liao WC, Chang CH
TitleEnantiomeric inhibitors of cholesterol esterase and acetylcholinesterase.
[4]
Commentscatalysis
PubMed ID10433704
JournalBiochemistry
Year1999
Volume38
Pages9971-81
AuthorsLin G, Shieh CT, Ho HC, Chouhwang JY, Lin WY, Lu CP
TitleStructure-reactivity relationships for the inhibition mechanism at the second alkyl-chain-binding site of cholesterol esterase and lipase.
[5]
Commentscatalysis
PubMed ID10350625
JournalBiochim Biophys Acta
Year1999
Volume1431
Pages500-11
AuthorsLin G, Shieh CT, Tsai YC, Hwang CI, Lu CP, Chen GH
TitleStructure-reactivity probes for active site shapes of cholesterol esterase by carbamate inhibitors.
[6]
Commentscatalysis (inhibition)
PubMed ID10514295
JournalJ Med Chem
Year1999
Volume42
Pages4250-6
AuthorsDeck LM, Baca ML, Salas SL, Hunsaker LA, Vander Jagt DL
Title3-Alkyl-6-chloro-2-pyrones: selective inhibitors of pancreatic cholesterol esterase.
[7]
Commentscatalysis (structure-activity relationships)
PubMed ID11092545
JournalBioorg Med Chem
Year2000
Volume8
Pages2601-7
AuthorsLin G, Liao WC, Chiou SY
TitleQuantitative structure-activity relationships for the pre-steady-state inhibition of cholesterol esterase by 4-nitrophenyl-N-substituted carbamates.
[8]
PubMed ID11045623
JournalProtein Sci
Year2000
Volume9
Pages1783-90
AuthorsTerzyan S, Wang CS, Downs D, Hunter B, Zhang XC
TitleCrystal structure of the catalytic domain of human bile salt activated lipase.
Related PDB1f6w
[9]
Commentscatalysis
PubMed ID11738092
JournalBiochim Biophys Acta
Year2001
Volume1550
Pages100-6
AuthorsSmith RE, Burmaster S, Glaros AG, Eick JD, Walde P, Kostoryz EL, Yourtee DM
TitleAromatic dental monomers affect the activity of cholesterol esterase.
[10]
Commentscatalysis
PubMed ID11453726
JournalChem Res Toxicol
Year2001
Volume14
Pages807-13
AuthorsDoorn JA, Talley TT, Thompson CM, Richardson RJ
TitleProbing the active sites of butyrylcholinesterase and cholesterol esterase with isomalathion: conserved stereoselective inactivation of serine hydrolases structurally related to acetylcholinesterase.
[11]
Commentscatalysis (mutation analysis)
PubMed ID11429416
JournalJ Biol Chem
Year2001
Volume276
Pages33165-74
AuthorsWallace TJ, Kodsi EM, Langston TB, Gergis MR, Grogan WM
TitleMutation of residues 423 (Met/Ile), 444 (Thr/Met), and 506 (Asn/Ser) confer cholesteryl esterase activity on rat lung carboxylesterase. Ser-506 is required for activation by cAMP-dependent protein kinase.
[12]
CommentsX-ray crystallography (2.6 Angstroms; truncated variant), catalysis
PubMed ID11563913
JournalJ Mol Biol
Year2001
Volume312
Pages511-23
AuthorsMoore SA, Kingston RL, Loomes KM, Hernell O, Blackberg L, Baker HM, Baker EN
TitleThe structure of truncated recombinant human bile salt-stimulated lipase reveals bile salt-independent conformational flexibility at the active-site loop and provides insights into heparin binding.
Related PDB1jmy

comments
Although Asp437 (1aql) is annotated as catalytic residue in Swiss-prot (BAL_BOVIN;P30122), His435 (1aql) is more likely to be the residue, which is conserved throughout in the superfamily. This is supported by the literature ([1] & [2]).
According to the literature [2], this enzyme hydrolyzes both water soluble and hydrophobic esters, and its structure suggests that it can be evolutionarily between the triglyceride lipases and the esterases. The triglyseride lipases prefentially hydrolyze hydrophobic esters and lipids, while esterases such as acetylcholinesterase work on water soluble substrates.
This paper [2] also suggests that the nucleophilic attack takes place from the opposite side of the ester, leading to the inversion of chirality of the tetrahedral intermediate with respect to the trypsin-like serine proteases, where His435 acts as a base for the serine proton and then as an acid to the oxygen of the cholesterol leaving group, presenting both oxygens in a coplanar manner with the plane of the imidazole.
The paper [8] described the mechanism as follows: The catalysis consists of two steps of nucleophilic attack to the ester bond of the substrate. The first attack is by the catalytic residue Ser194, and the second one by a nearby water molecule. The first reaction step releases the alcoholic product, and the second step releases the fatty acid.

createdupdated
2002-07-302012-10-22


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
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 2010)
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)

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