3jw8

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of human mono-glyceride lipase

Structural highlights

3jw8 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.
Method:	X-ray diffraction, Resolution 2.1Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MGLL_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/3jw8"

@@ Line 1: / Line 1: @@
 ==Crystal structure of human mono-glyceride lipase==
-<StructureSection load='3jw8' size='340' side='right' caption='[[3jw8]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
+<StructureSection load='3jw8' size='340' side='right'caption='[[3jw8]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3jw8]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3JW8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3JW8 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3jw8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3JW8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3JW8 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</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]] 2.1&#8491;</td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3jwe|3jwe]]</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=3jw8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jw8 OCA], [https://pdbe.org/3jw8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3jw8 RCSB], [https://www.ebi.ac.uk/pdbsum/3jw8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3jw8 ProSAT]</span></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 HUMAN])</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 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=3jw8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jw8 OCA], [http://pdbe.org/3jw8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3jw8 RCSB], [http://www.ebi.ac.uk/pdbsum/3jw8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3jw8 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/MGLL_HUMAN MGLL_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>
+[https://www.uniprot.org/uniprot/MGLL_HUMAN MGLL_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 18: / Line 15: @@
   <jmolCheckbox>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jw/3jw8_consurf.spt"</scriptWhenChecked>
-    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
@@ Line 34: / Line 31: @@
 ==See Also==
-*[[Lipase|Lipase]]
+*[[Lipase 3D Structures|Lipase 3D Structures]]
-*[[Monoglyceride lipase|Monoglyceride lipase]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Acylglycerol lipase]]
+[[Category: Homo sapiens]]
-[[Category: Human]]
+[[Category: Large Structures]]
-[[Category: Auge, F]]
+[[Category: Auge F]]
-[[Category: Berne, P F]]
+[[Category: Berne PF]]
-[[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]]

3jw8

From Proteopedia

Current revision

Crystal structure of human mono-glyceride lipase

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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