DB code: S00347

RLCP classification 1.12.30000.10 : Hydrolysis
CATH domain 3.40.50.1820 : Rossmann fold Catalytic domain
E.C. 3.1.1.3 3.1.1.13
CSA 1aql
M-CSA 1aql
MACiE

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

Uniprot Enzyme Name
UniprotKB Protein name Synonyms MEROPS Pfam
P30122 Bile salt-activated lipase
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
S09.985 (Serine)
PF00135 (COesterase)
[Graphical View]
P19835 Bile salt-activated lipase
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
S09.985 (Serine)
PF00135 (COesterase)
[Graphical View]

KEGG enzyme name
triacylglycerol 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 )

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P30122 CEL_BOVIN Triacylglycerol + H(2)O = diacylglycerol + a carboxylate. A steryl ester + H(2)O = a sterol + a fatty acid.
P19835 CEL_HUMAN Triacylglycerol + H(2)O = diacylglycerol + a carboxylate. A steryl ester + H(2)O = a sterol + a fatty acid.

KEGG Pathways
Map code Pathways E.C.
MAP00120 Bile acid biosynthesis 3.1.1.13
MAP00561 Glycerolipid metabolism 3.1.1.3

Compound table
Substrates Products Intermediates
KEGG-id C00422 C01958 C00001 C00165 C00370 C00060 C00162 I00123 I00085 I00086
E.C. 3.1.1.3
3.1.1.13
3.1.1.3
3.1.1.13
3.1.1.3
3.1.1.13
3.1.1.3
3.1.1.13
3.1.1.3
3.1.1.13
3.1.1.3
3.1.1.13
3.1.1.3
3.1.1.13
Compound Triacylglycerol Steryl ester H2O Diacylglycerol Sterol Carboxylate Fatty acid Peptidyl-Ser-tetrahedral intermediate (with previous carboxylic-ester) Acyl-enzyme(Peptidyl-Ser-acyl group) Peptidyl-Ser-tetrahedral-intermediate
Type carbohydrate,lipid carbohydrate,steroid H2O carbohydrate,lipid carbohydrate,steroid carboxyl group fatty acid
ChEBI 15377
PubChem 22247451
962
1107
1aqlA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Analogue:2xTCH Unbound Unbound Unbound Unbound Unbound
1aqlB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Analogue:2xTCH Unbound Unbound Unbound Unbound Unbound
2bceA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1aknA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1f6wA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1jmyA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1aqlA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 194;ASP 320;HIS 435 GLY 107;ALA 195
1aqlB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 194;ASP 320;HIS 435 GLY 107;ALA 195
2bceA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 194;ASP 320;HIS 435 GLY 107;ALA 195
1aknA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 194;ASP 320;HIS 435 GLY 107;ALA 195
1f6wA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 194;ASP 320;HIS 435 GLY 107;ALA 195
1jmyA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 194;ASP 320;HIS 435 GLY 107;ALA 195

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[2]
p.5116, Fig.9 4
[4]
Fig.5
[5]
Fig.1
[7]
Fig.4
[8]
p.1787

References
[1]
Resource
Comments X-ray crystallography (2.8 Angstroms)
Medline ID
PubMed ID 9331420
Journal Structure
Year 1997
Volume 5
Pages 1209-18
Authors Wang X, Wang CS, Tang J, Dyda F, Zhang XC
Title The crystal structure of bovine bile salt activated lipase: insights into the bile salt activation mechanism.
Related PDB 1aql 1akn
Related UniProtKB
[2]
Resource
Comments X-ray crystallography (1.6 Angstroms), catalysis
Medline ID
PubMed ID 9548741
Journal Biochemistry
Year 1998
Volume 37
Pages 5107-17
Authors Chen JC, Miercke LJ, Krucinski J, Starr JR, Saenz G, Wang X, Spilburg CA, Lange LG, Ellsworth JL, Stroud RM
Title Structure of bovine pancreatic cholesterol esterase at 1.6 A: novel structural features involved in lipase activation.
Related PDB 2bce
Related UniProtKB
[3]
Resource
Comments catalysis (inhibitor)
Medline ID
PubMed ID 9774723
Journal Biochim Biophys Acta
Year 1998
Volume 1388
Pages 161-74
Authors Lin G, Tsai YC, Liu HC, Liao WC, Chang CH
Title Enantiomeric inhibitors of cholesterol esterase and acetylcholinesterase.
Related PDB
Related UniProtKB
[4]
Resource
Comments catalysis
Medline ID
PubMed ID 10433704
Journal Biochemistry
Year 1999
Volume 38
Pages 9971-81
Authors Lin G, Shieh CT, Ho HC, Chouhwang JY, Lin WY, Lu CP
Title Structure-reactivity relationships for the inhibition mechanism at the second alkyl-chain-binding site of cholesterol esterase and lipase.
Related PDB
Related UniProtKB
[5]
Resource
Comments catalysis
Medline ID
PubMed ID 10350625
Journal Biochim Biophys Acta
Year 1999
Volume 1431
Pages 500-11
Authors Lin G, Shieh CT, Tsai YC, Hwang CI, Lu CP, Chen GH
Title Structure-reactivity probes for active site shapes of cholesterol esterase by carbamate inhibitors.
Related PDB
Related UniProtKB
[6]
Resource
Comments catalysis (inhibition)
Medline ID
PubMed ID 10514295
Journal J Med Chem
Year 1999
Volume 42
Pages 4250-6
Authors Deck LM, Baca ML, Salas SL, Hunsaker LA, Vander Jagt DL
Title 3-Alkyl-6-chloro-2-pyrones: selective inhibitors of pancreatic cholesterol esterase.
Related PDB
Related UniProtKB
[7]
Resource
Comments catalysis (structure-activity relationships)
Medline ID
PubMed ID 11092545
Journal Bioorg Med Chem
Year 2000
Volume 8
Pages 2601-7
Authors Lin G, Liao WC, Chiou SY
Title Quantitative structure-activity relationships for the pre-steady-state inhibition of cholesterol esterase by 4-nitrophenyl-N-substituted carbamates.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 11045623
Journal Protein Sci
Year 2000
Volume 9
Pages 1783-90
Authors Terzyan S, Wang CS, Downs D, Hunter B, Zhang XC
Title Crystal structure of the catalytic domain of human bile salt activated lipase.
Related PDB 1f6w
Related UniProtKB
[9]
Resource
Comments catalysis
Medline ID
PubMed ID 11738092
Journal Biochim Biophys Acta
Year 2001
Volume 1550
Pages 100-6
Authors Smith RE, Burmaster S, Glaros AG, Eick JD, Walde P, Kostoryz EL, Yourtee DM
Title Aromatic dental monomers affect the activity of cholesterol esterase.
Related PDB
Related UniProtKB
[10]
Resource
Comments catalysis
Medline ID
PubMed ID 11453726
Journal Chem Res Toxicol
Year 2001
Volume 14
Pages 807-13
Authors Doorn JA, Talley TT, Thompson CM, Richardson RJ
Title Probing the active sites of butyrylcholinesterase and cholesterol esterase with isomalathion: conserved stereoselective inactivation of serine hydrolases structurally related to acetylcholinesterase.
Related PDB
Related UniProtKB
[11]
Resource
Comments catalysis (mutation analysis)
Medline ID
PubMed ID 11429416
Journal J Biol Chem
Year 2001
Volume 276
Pages 33165-74
Authors Wallace TJ, Kodsi EM, Langston TB, Gergis MR, Grogan WM
Title Mutation 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.
Related PDB
Related UniProtKB
[12]
Resource
Comments X-ray crystallography (2.6 Angstroms; truncated variant), catalysis
Medline ID
PubMed ID 11563913
Journal J Mol Biol
Year 2001
Volume 312
Pages 511-23
Authors Moore SA, Kingston RL, Loomes KM, Hernell O, Blackberg L, Baker HM, Baker EN
Title The 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 PDB 1jmy
Related UniProtKB

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.

Created Updated
2002-07-30 2012-10-22