Protein science, 2011-04, Vol.20 (4), p.670-683
- Schalk‐Hihi, Céline
- Schubert, Carsten
- Alexander, Richard
- Bayoumy, Shariff
- Clemente, Jose C.
- Deckman, Ingrid
- DesJarlais, Renee L.
- Dzordzorme, Keli C.
- Flores, Christopher M.
- Grasberger, Bruce
- Kranz, James K.
- Lewandowski, Frank
- Liu, Li
- Ma, Hongchang
- Maguire, Diane
- Macielag, Mark J.
- McDonnell, Mark E.
- Mezzasalma Haarlander, Tara
- Miller, Robyn
- Milligan, Cindy
- Reynolds, Charles
- Kuo, Lawrence C.
2011
Details
- Autor(en) / Beteiligte
- Schalk‐Hihi, Céline
- Schubert, Carsten
- Alexander, Richard
- Bayoumy, Shariff
- Clemente, Jose C.
- Deckman, Ingrid
- DesJarlais, Renee L.
- Dzordzorme, Keli C.
- Flores, Christopher M.
- Grasberger, Bruce
- Kranz, James K.
- Lewandowski, Frank
- Liu, Li
- Ma, Hongchang
- Maguire, Diane
- Macielag, Mark J.
- McDonnell, Mark E.
- Mezzasalma Haarlander, Tara
- Miller, Robyn
- Milligan, Cindy
- Reynolds, Charles
- Kuo, Lawrence C.
- Titel
- Crystal structure of a soluble form of human monoglyceride lipase in complex with an inhibitor at 1.35 Å resolution
- Ist Teil von
- Protein science, 2011-04, Vol.20 (4), p.670-683
- Ort / Verlag
- Hoboken: Wiley Subscription Services, Inc., A Wiley Company
- Erscheinungsjahr
- 2011
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- A high‐resolution structure of a ligand‐bound, soluble form of human monoglyceride lipase (MGL) is presented. The structure highlights a novel conformation of the regulatory lid‐domain present in the lipase family as well as the binding mode of a pharmaceutically relevant reversible inhibitor. Analysis of the structure lacking the inhibitor indicates that the closed conformation can accommodate the native substrate 2‐arachidonoyl glycerol. A model is proposed in which MGL undergoes conformational and electrostatic changes during the catalytic cycle ultimately resulting in its dissociation from the membrane upon completion of the cycle. In addition, the study outlines a successful approach to transform membrane associated proteins, which tend to aggregate upon purification, into a monomeric and soluble form. PDB Code(s): 3PE6
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0961-8368eISSN: 1469-896XDOI: 10.1002/pro.596Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3081545
- Format
- –
- Schlagworte
- 60 APPLIED LIFE SCIENCES, Arachidonic Acids - chemistry, Arachidonic Acids - metabolism, BASIC BIOLOGICAL SCIENCES, Binding sites, cannabinoid receptor, Cannabinoid Receptor Modulators - chemistry, Cannabinoid Receptor Modulators - metabolism, Catalytic Domain, CRYSTAL STRUCTURE, Crystallography, X-Ray, DISSOCIATION, ELECTROSTATICS, Endocannabinoids, Glycerides - chemistry, Glycerides - metabolism, GLYCEROL, Humans, lid‐domain, LIPASES, MEMBRANES, Models, Molecular, Molecular Sequence Data, Molecular Structure, Monoacylglycerol Lipases - antagonists & inhibitors, Monoacylglycerol Lipases - chemistry, Monoacylglycerol Lipases - genetics, Monoacylglycerol Lipases - metabolism, monoglyceride lipase, Mutagenesis, Site-Directed, Protein Binding, protein inhibitor complex, Protein Structure, Secondary, Protein Structure, Tertiary, PROTEINS, PURIFICATION, RESOLUTION, Static Electricity, SUBSTRATES