3uuf

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Crystal structure of mono- and diacylglycerol lipase from Malassezia globosa

Structural highlights

3uuf is a 1 chain structure with sequence from Malassezia globosa CBS 7966. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.6Å
Ligands:MAN, NAG
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

LIP1_MALGO Secreted lipase involved in Dandruff and seborrheic dermatitis (D/SD) probably via lipase-mediated breakdown of sebaceous lipids and release of irritating free fatty acids (PubMed:17460728, PubMed:18000048). Shows activity against monoglyceride and diglyceride substrates, but not triglyceride substrates and does not exhibit regio-selective production of diacylglycerols (PubMed:17460728, PubMed:22750000, PubMed:25837472, PubMed:25955297, PubMed:26239010, PubMed:26365206, PubMed:27130210). Able to hydrolyze diacylglycerols such as distearin, dilinolein, dipalmitoylglycerol and dipalmitolein (PubMed:27130210). Cleaves oleic acid from 1,2 isomers of diolein on both the 1 and the 2 position of the glycerol backbone, resulting mainly in free fatty acids but no monoolein is detected (PubMed:27130210). Shows activity on monoolein and liberates mostly free fatty acids, but can also perform the reverse reaction and produce diolein (PubMed:27130210).[1] [2] [3] [4] [5] [6] [7] [8]

Publication Abstract from PubMed

Most lipases contain a lid domain to shield the hydrophobic binding site from the water environment. The lid, mostly in helical form, can undergo a conformational change to expose the active cleft during the interfacial activation. Here we report the crystal structures of Malassezia globosa LIP1 (SMG1) at 1.45 and 2.60A resolution in two crystal forms. The structures present SMG1 in its closed form, with a novel lid in loop conformation. SMG1 is one of the few members in the fungal lipase family that has been found to be strictly specific for mono- and diacylglycerol. To date, the mechanism for this substrate specificity remains largely unknown. To investigate the substrate binding properties, we built a model of SMG1 in open conformation. Based on this model, we found that the two bulky hydrophobic residues adjacent to the catalytic site and the N-terminal hinge region of the lid both may act as steric hindrances for triacylglycerols binding. These unique structural features of SMG1 will provide a better understanding on the substrate specificity of mono- and diacylglycerol lipases and a platform for further functional study of this enzyme.

Crystal structure of a mono- and diacylglycerol lipase from Malassezia globosa reveals a novel lid conformation and insights into the substrate specificity.,Xu T, Liu L, Hou S, Xu J, Yang B, Wang Y, Liu J J Struct Biol. 2012 Mar 29. PMID:22484238[9]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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See Also

References

  1. ↑ DeAngelis YM, Saunders CW, Johnstone KR, Reeder NL, Coleman CG, Kaczvinsky JR Jr, Gale C, Walter R, Mekel M, Lacey MP, Keough TW, Fieno A, Grant RA, Begley B, Sun Y, Fuentes G, Youngquist RS, Xu J, Dawson TL Jr. Isolation and expression of a Malassezia globosa lipase gene, LIP1. J Invest Dermatol. 2007 Sep;127(9):2138-46. PMID:17460728 doi:10.1038/sj.jid.5700844
  2. ↑ Xu J, Saunders CW, Hu P, Grant RA, Boekhout T, Kuramae EE, Kronstad JW, Deangelis YM, Reeder NL, Johnstone KR, Leland M, Fieno AM, Begley WM, Sun Y, Lacey MP, Chaudhary T, Keough T, Chu L, Sears R, Yuan B, Dawson TL Jr. Dandruff-associated Malassezia genomes reveal convergent and divergent virulence traits shared with plant and human fungal pathogens. Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18730-5. PMID:18000048 doi:10.1073/pnas.0706756104
  3. ↑ Liu L, Gao C, Lan D, Yang B, Wang Y. Molecular basis for substrate selectivity of a mono from Malassezia globosa. Biochem Biophys Res Commun. 2012 Jul 27;424(2):285-9. PMID:22750000 doi:10.1016/j.bbrc.2012.06.108
  4. ↑ Lan D, Wang Q, Xu J, Zhou P, Yang B, Wang Y. Residue Asn277 affects the stability and substrate specificity of the SMG1 lipase from Malassezia globosa. Int J Mol Sci. 2015 Mar 31;16(4):7273-88. PMID:25837472 doi:10.3390/ijms16047273
  5. ↑ Lan D, Popowicz GM, Pavlidis IV, Zhou P, Bornscheuer UT, Wang Y. Conversion of a Mono Protein Engineering. Chembiochem. 2015 Jul 6;16(10):1431-4. PMID:25955297 doi:10.1002/cbic.201500163
  6. ↑ Lan D, Wang Q, Popowicz GM, Yang B, Tang Q, Wang Y. The Role of Residues 103, 104, and 278 in the Activity of SMG1 Lipase from Malassezia globosa: A Site-Directed Mutagenesis Study. J Microbiol Biotechnol. 2015 Nov;25(11):1827-34. PMID:26239010 doi:10.4014/jmb.1506.06079
  7. ↑ Guo S, Xu J, Pavlidis IV, Lan D, Bornscheuer UT, Liu J, Wang Y. Structure of product-bound SMG1 lipase: active site gating implications. FEBS J. 2015 Sep 13. doi: 10.1111/febs.13513. PMID:26365206 doi:http://dx.doi.org/10.1111/febs.13513
  8. ↑ Sommer B, Overy DP, Haltli B, Kerr RG. Secreted lipases from Malassezia globosa: recombinant expression and determination of their substrate specificities. Microbiology (Reading). 2016 Jul;162(7):1069-1079. PMID:27130210 doi:10.1099/mic.0.000299
  9. ↑ Xu T, Liu L, Hou S, Xu J, Yang B, Wang Y, Liu J. Crystal structure of a mono- and diacylglycerol lipase from Malassezia globosa reveals a novel lid conformation and insights into the substrate specificity. J Struct Biol. 2012 Mar 29. PMID:22484238 doi:10.1016/j.jsb.2012.03.006

Contents


PDB ID 3uuf

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