|
|
| CATH domain | Related DB codes (homologues) |
|---|
| 3.40.50.1820 | 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 |
| Swiss-prot:Accession Number | P30122 | P19835 |
|---|
| Entry name | CEL_BOVIN | CEL_HUMAN |
|---|
| Activity | Triacylglycerol + 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 |
|
|
|---|
| 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] |
|---|
| Comments | X-ray crystallography (2.8 Angstroms) |
|---|
| 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 |
|---|
| [2] |
|---|
| Comments | X-ray crystallography (1.6 Angstroms), catalysis |
|---|
| 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 |
|---|
| [3] |
|---|
| Comments | catalysis (inhibitor) |
|---|
| 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. |
|---|
| [4] |
|---|
| Comments | catalysis |
|---|
| 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. |
|---|
| [5] |
|---|
| Comments | catalysis |
|---|
| 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. |
|---|
| [6] |
|---|
| Comments | catalysis (inhibition) |
|---|
| 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. |
|---|
| [7] |
|---|
| Comments | catalysis (structure-activity relationships) |
|---|
| 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. |
|---|
| [8] |
|---|
| 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 |
|---|
| [9] |
|---|
| Comments | catalysis |
|---|
| 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. |
|---|
| [10] |
|---|
| Comments | catalysis |
|---|
| 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. |
|---|
| [11] |
|---|
| Comments | catalysis (mutation analysis) |
|---|
| 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. |
|---|
| [12] |
|---|
| Comments | X-ray crystallography (2.6 Angstroms; truncated variant), catalysis |
|---|
| 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 |
|---|
| 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 |
|
|
