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 15377
PubChem								22247451 962 22247451 962		1107 1107
1aqlA						Unbound	Unbound		Unbound	Analogue:2xTCH	Unbound	Unbound	Unbound	Unbound	Unbound
1aqlB						Unbound	Unbound		Unbound	Analogue:2xTCH	Unbound	Unbound	Unbound	Unbound	Unbound
2bceA						Unbound	Unbound		Unbound	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1aknA						Unbound	Unbound		Unbound	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1f6wA						Unbound	Unbound		Unbound	Unbound	Unbound	Unbound	Unbound	Unbound	Unbound
1jmyA						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						SER 194;ASP 320;HIS 435			GLY 107;ALA 195
1aqlB						SER 194;ASP 320;HIS 435			GLY 107;ALA 195
2bceA						SER 194;ASP 320;HIS 435			GLY 107;ALA 195
1aknA						SER 194;ASP 320;HIS 435			GLY 107;ALA 195
1f6wA						SER 194;ASP 320;HIS 435			GLY 107;ALA 195
1jmyA						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