3jwe

From Proteopedia

(Difference between revisions)

Revision as of 07:40, 24 December 2014

Crystal structure of human mono-glyceride lipase in complex with SAR629

Structural highlights

3jwe is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	MGLL, hCG_40840 (Homo sapiens)
Activity:	Acylglycerol lipase, with EC number 3.1.1.23
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[Q6IBG9_HUMAN] Converts monoacylglycerides to free fatty acids and glycerol. Hydrolyzes the endocannabinoid 2-arachidonoylglycerol, and thereby contributes to the regulation of endocannabinoid signaling, nociperception and perception of pain (By similarity). Regulates the levels of fatty acids that serve as signaling molecules and promote cancer cell migration, invasion and tumor growth.^[1]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Monoglyceride lipase (MGL) is a serine hydrolase that hydrolyses 2-arachidonoylglycerol (2-AG) into arachidonic acid and glycerol. 2-AG is an endogenous ligand of cannabinoid receptors, involved in various physiological processes in the brain. We present here the first crystal structure of human MGL in its apo form and in complex with the covalent inhibitor SAR629. MGL shares the classic fold of the alpha/beta hydrolase family but depicts an unusually large hydrophobic occluded tunnel with a highly flexible lid at its entry and the catalytic triad buried at its end. Structures reveal the configuration of the catalytic triad and the shape and nature of the binding site of 2-AG. The bound structure of SAR629 highlights the key interactions for productive binding with MGL. The shape of the tunnel suggests a high druggability of the protein and provides an attractive template for drug discovery.

Structural basis for human monoglyceride lipase inhibition.,Bertrand T, Auge F, Houtmann J, Rak A, Vallee F, Mikol V, Berne PF, Michot N, Cheuret D, Hoornaert C, Mathieu M J Mol Biol. 2010 Feb 26;396(3):663-73. Epub 2009 Dec 3. PMID:19962385^[2]

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

References

↑ Nomura DK, Long JZ, Niessen S, Hoover HS, Ng SW, Cravatt BF. Monoacylglycerol lipase regulates a fatty acid network that promotes cancer pathogenesis. Cell. 2010 Jan 8;140(1):49-61. doi: 10.1016/j.cell.2009.11.027. PMID:20079333 doi:10.1016/j.cell.2009.11.027
↑ Bertrand T, Auge F, Houtmann J, Rak A, Vallee F, Mikol V, Berne PF, Michot N, Cheuret D, Hoornaert C, Mathieu M. Structural basis for human monoglyceride lipase inhibition. J Mol Biol. 2010 Feb 26;396(3):663-73. Epub 2009 Dec 3. PMID:19962385 doi:10.1016/j.jmb.2009.11.060

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3jwe"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[3jwe]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3JWE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3JWE FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=F4P:1-[BIS(4-FLUOROPHENYL)METHYL]-4-(1H-1,2,4-TRIAZOL-1-YLCARBONYL)PIPERAZINE'>F4P</scene><br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=F4P:1-[BIS(4-FLUOROPHENYL)METHYL]-4-(1H-1,2,4-TRIAZOL-1-YLCARBONYL)PIPERAZINE'>F4P</scene></td></tr>
-<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MGLL, hCG_40840 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MGLL, hCG_40840 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Acylglycerol_lipase Acylglycerol lipase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.23 3.1.1.23] </span></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Acylglycerol_lipase Acylglycerol lipase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.23 3.1.1.23] </span></td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3jwe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jwe OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3jwe RCSB], [http://www.ebi.ac.uk/pdbsum/3jwe PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3jwe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jwe OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3jwe RCSB], [http://www.ebi.ac.uk/pdbsum/3jwe PDBsum]</span></td></tr>
-<table>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/Q6IBG9_HUMAN Q6IBG9_HUMAN]] Converts monoacylglycerides to free fatty acids and glycerol. Hydrolyzes the endocannabinoid 2-arachidonoylglycerol, and thereby contributes to the regulation of endocannabinoid signaling, nociperception and perception of pain (By similarity). Regulates the levels of fatty acids that serve as signaling molecules and promote cancer cell migration, invasion and tumor growth.<ref>PMID:20079333</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 36: / Line 38: @@
 [[Category: Acylglycerol lipase]]
 [[Category: Homo sapiens]]
-[[Category: Auge, F.]]
+[[Category: Auge, F]]
-[[Category: Berne, P F.]]
+[[Category: Berne, P F]]
-[[Category: Bertrand, T.]]
+[[Category: Bertrand, T]]
-[[Category: Cheuret, D.]]
+[[Category: Cheuret, D]]
-[[Category: Hoornaert, C.]]
+[[Category: Hoornaert, C]]
-[[Category: Houtmann, J.]]
+[[Category: Houtmann, J]]
-[[Category: Mathieu, M.]]
+[[Category: Mathieu, M]]
-[[Category: Michot, N.]]
+[[Category: Michot, N]]
-[[Category: Mikol, V.]]
+[[Category: Mikol, V]]
-[[Category: Rak, A.]]
+[[Category: Rak, A]]
-[[Category: Vallee, F.]]
+[[Category: Vallee, F]]
 [[Category: Alpha-beta hydrolase]]
 [[Category: Hydrolase]]

3jwe

From Proteopedia

Revision as of 07:40, 24 December 2014

Crystal structure of human mono-glyceride lipase in complex with SAR629

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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