Structural highlights
Function
[LIP_STRRM] Catalyzes the hydrolysis of p-nitrophenyl esters, alpha- and beta-naphthyl esters, and triacylglycerols, with a preference for medium acyl chain length (C8-C12). Shows a much higher hydrolysis rate of glycerol esters of unsaturated C16 and C18 fatty acids than that of their saturated counterparts, and a preference for cis double bond. Is also able to hydrolyze several natural oils and Tween detergents. Also displays thioesterase and phospholipase activities, towards palmitoyl-coenzyme A and diheptanoyl glycerophosphocholine, respectively. Shows transesterification activity of racemic 1-phenyl ethanol with vinyl acetate in hexane, proceeding with partial (R)-enantioselectivity.[1] [2] [REFERENCE:5]
Publication Abstract from PubMed
SrLip is an extracellular enzyme from Streptomyces rimosus (Q93MW7) exhibiting lipase, phospholipase, esterase, thioesterase, and tweenase activities. The structure of SrLip is one of a very few lipases, among the 3D-structures of the SGNH superfamily of hydrolases, structurally characterized by synchrotron diffraction data at 1.75 A resolution (PDB: 5MAL ). Its crystal structure was determined by molecular replacement using a homology model based on the crystal structure of phospholipase A1 from Streptomyces albidoflavus (PDB: 4HYQ ). The structure reveals the Rossmann-like 3-layer alphabetaalpha sandwich fold typical of the SGNH superfamily stabilized by three disulfide bonds. The active site shows a catalytic dyad involving Ser10 and His216 with Ser10-OgammaH...NepsilonHis216, His216-NdeltaH...O horizontal lineC-Ser214, and Gly54-NH...Ogamma-Ser10 hydrogen bonds essential for the catalysis; the carbonyl oxygen of the Ser214 main chain acts as a hydrogen bond acceptor ensuring the orientation of the His216 imidazole ring suitable for a proton transfer. Molecular dynamics simulations of the apoenzyme and its complex with p-nitrophenyl caprylate were used to probe the positioning of the substrate ester group within the active site and its aliphatic chain within the binding site. Quantum-mechanical calculations at the DFT level revealed the precise molecular mechanism of the SrLip catalytic activity, demonstrating that the overall hydrolysis is a two-step process with acylation as the rate-limiting step associated with the activation free energy of DeltaGENZ = 17.9 kcal mol-1, being in reasonable agreement with the experimental value of 14.5 kcal mol-1, thus providing strong support in favor of the proposed catalytic mechanism based on a dyad.
Catalytic Dyad in the SGNH Hydrolase Superfamily: In-depth Insight into Structural Parameters Tuning the Catalytic Process of Extracellular Lipase from Streptomyces rimosus.,Lescic Asler I, Stefanic Z, Marsavelski A, Vianello R, Kojic-Prodic B ACS Chem Biol. 2017 Jul 21;12(7):1928-1936. doi: 10.1021/acschembio.6b01140. Epub, 2017 Jun 14. PMID:28558229[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lescic Asler I, Ivic N, Kovacic F, Schell S, Knorr J, Krauss U, Wilhelm S, Kojic-Prodic B, Jaeger KE. Probing enzyme promiscuity of SGNH hydrolases. Chembiochem. 2010 Oct 18;11(15):2158-67. doi: 10.1002/cbic.201000398. PMID:20931591 doi:10.1002/cbic.201000398
- ↑ Lescic Asler I, Ivic N, Kovacic F, Schell S, Knorr J, Krauss U, Wilhelm S, Kojic-Prodic B, Jaeger KE. Probing enzyme promiscuity of SGNH hydrolases. Chembiochem. 2010 Oct 18;11(15):2158-67. doi: 10.1002/cbic.201000398. PMID:20931591 doi:10.1002/cbic.201000398
- ↑ Lescic Asler I, Stefanic Z, Marsavelski A, Vianello R, Kojic-Prodic B. Catalytic Dyad in the SGNH Hydrolase Superfamily: In-depth Insight into Structural Parameters Tuning the Catalytic Process of Extracellular Lipase from Streptomyces rimosus. ACS Chem Biol. 2017 Jul 21;12(7):1928-1936. doi: 10.1021/acschembio.6b01140. Epub, 2017 Jun 14. PMID:28558229 doi:http://dx.doi.org/10.1021/acschembio.6b01140
