4zre

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of SMG1 F278D mutant

Structural highlights

4zre 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 2Å
Ligands:	, ,
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

Monoacylglycerol and diacylglycerol lipases are industrially interesting enzymes, due to the health benefits that arise from the consumption of diglycerides compared to the traditional triglyceride oils. Most lipases possess an alpha-helix (lid) directly over the catalytic pocket which regulates the activity of the enzyme. Generally, lipases exist in active and inactive conformations, depending on the positioning of this lid subdomain. However, lipase SMG1, a monoacylglycerol and diacylglycerol specific lipase, has an atypical activation mechanism. In the present study we were able to prove by crystallography, in silico analysis and activity tests that only two positions, residues 102 and 278, are responsible for a gating mechanism that regulates the active and inactive states of the lipase, and that no significant structural changes take place during activation except for oxyanion hole formation. The elucidation of the gating effect provided data enabling the rational design of improved lipases with 6-fold increase in the hydrolytic activity toward diacylglycerols, just by providing additional substrate stabilization with a single mutation (F278N or F278T). Due to the conservation of F278 among the monoacylglycerol and diacylglycerol lipases in the Rhizomucor miehei lipase-like family, the gating mechanism described herein might represent a general mechanism applicable to other monoacylglycerol and diacylglycerol lipases as well. DATABASE: Structural data are available in the Protein Data Bank under the accession numbers 4ZRE (F278D mutant) and 4ZRD (F278N mutant).

Structure of product-bound SMG1 lipase: active site gating implications.,Guo S, Xu J, Pavlidis IV, Lan D, Bornscheuer UT, Liu J, Wang Y FEBS J. 2015 Sep 13. doi: 10.1111/febs.13513. PMID:26365206^[9]

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

References

↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4zre"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4zre]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Malassezia_globosa_CBS_7966 Malassezia globosa CBS 7966]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZRE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZRE FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4zre FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zre OCA], [https://pdbe.org/4zre PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zre RCSB], [https://www.ebi.ac.uk/pdbsum/4zre PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zre ProSAT]</span></td></tr>
 </table>
 == Function ==
-[https://www.uniprot.org/uniprot/A8PUY1_MALGO A8PUY1_MALGO]
+[https://www.uniprot.org/uniprot/LIP1_MALGO 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).<ref>PMID:17460728</ref> <ref>PMID:18000048</ref> <ref>PMID:22750000</ref> <ref>PMID:25837472</ref> <ref>PMID:25955297</ref> <ref>PMID:26239010</ref> <ref>PMID:26365206</ref> <ref>PMID:27130210</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

4zre

From Proteopedia

Current revision

Crystal structure of SMG1 F278D mutant

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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