1tl7: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1tl7.gif|left|200px]]< | [[Image:1tl7.gif|left|200px]] | ||
'''Complex Of Gs- With The Catalytic Domains Of Mammalian Adenylyl Cyclase: Complex With 2'(3')-O-(N-methylanthraniloyl)-guanosine 5'-triphosphate and Mn''' | {{Structure | ||
|PDB= 1tl7 |SIZE=350|CAPTION= <scene name='initialview01'>1tl7</scene>, resolution 2.80Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=GSP:5'-GUANOSINE-DIPHOSPHATE-MONOTHIOPHOSPHATE'>GSP</scene>, <scene name='pdbligand=FOK:FORSKOLIN'>FOK</scene> and <scene name='pdbligand=ONM:3'-O-(N-METHYLANTHRANILOYL)-GUANOSINE-5'-TRIPHOSPHATE'>ONM</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Adenylate_cyclase Adenylate cyclase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.6.1.1 4.6.1.1] | |||
|GENE= Name=ADCY5; ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9615 Canis lupus familiaris]), Name=Adcy2; ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus]), Name=GNAS; Synonyms=GNAS1; ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 Bos taurus]) | |||
}} | |||
'''Complex Of Gs- With The Catalytic Domains Of Mammalian Adenylyl Cyclase: Complex With 2'(3')-O-(N-methylanthraniloyl)-guanosine 5'-triphosphate and Mn''' | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
1TL7 is a [ | 1TL7 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [http://en.wikipedia.org/wiki/Canis_lupus_familiaris Canis lupus familiaris] and [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TL7 OCA]. | ||
==Reference== | ==Reference== | ||
Structural basis for the inhibition of mammalian membrane adenylyl cyclase by 2 '(3')-O-(N-Methylanthraniloyl)-guanosine 5 '-triphosphate., Mou TC, Gille A, Fancy DA, Seifert R, Sprang SR, J Biol Chem. 2005 Feb 25;280(8):7253-61. Epub 2004 Dec 9. PMID:[http:// | Structural basis for the inhibition of mammalian membrane adenylyl cyclase by 2 '(3')-O-(N-Methylanthraniloyl)-guanosine 5 '-triphosphate., Mou TC, Gille A, Fancy DA, Seifert R, Sprang SR, J Biol Chem. 2005 Feb 25;280(8):7253-61. Epub 2004 Dec 9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15591060 15591060] | ||
[[Category: Adenylate cyclase]] | [[Category: Adenylate cyclase]] | ||
[[Category: Bos taurus]] | [[Category: Bos taurus]] | ||
| Line 30: | Line 39: | ||
[[Category: mant-gtp]] | [[Category: mant-gtp]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:19:49 2008'' | ||
Revision as of 15:19, 20 March 2008
| |||||||
| , resolution 2.80Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , , and | ||||||
| Gene: | Name=ADCY5; (Canis lupus familiaris), Name=Adcy2; (Rattus norvegicus), Name=GNAS; Synonyms=GNAS1; (Bos taurus) | ||||||
| Activity: | Adenylate cyclase, with EC number 4.6.1.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Complex Of Gs- With The Catalytic Domains Of Mammalian Adenylyl Cyclase: Complex With 2'(3')-O-(N-methylanthraniloyl)-guanosine 5'-triphosphate and Mn
OverviewOverview
Membrane-bound mammalian adenylyl cyclase (mAC) catalyzes the synthesis of intracellular cyclic AMP from ATP and is activated by stimulatory G protein alpha subunits (Galpha(s)) and by forskolin (FSK). mACs are inhibited with high potency by 2 '(3')-O-(N-methylanthraniloyl) (MANT)-substituted nucleotides. In this study, the crystal structures of the complex between Galpha(s).GTPgammaS and the catalytic C1 and C2 domains from type V and type II mAC (VC1.IIC2), bound to FSK and either MANT-GTP.Mg(2+) or MANT-GTP.Mn(2+) have been determined. MANT-GTP coordinates two metal ions and occupies the same position in the catalytic site as P-site inhibitors and substrate analogs. However, the orientation of the guanine ring is reversed relative to that of the adenine ring. The MANT fluorophore resides in a hydrophobic pocket at the interface between the VC1 and IIC2 domains and prevents mAC from undergoing the "open" to "closed" domain rearrangement. The K(i) of MANT-GTP for inhibition of VC1.IIC2 is lower in the presence of mAC activators and lower in the presence of Mn(2+) compared with Mg(2+), indicating that the inhibitor binds more tightly to the catalytically most active form of the enzyme. Fluorescence resonance energy transfer-stimulated emission from the MANT fluorophore upon excitation of Trp-1020 in the MANT-binding pocket of IIC2 is also stronger in the presence of FSK. Mutational analysis of two non-conserved amino acids in the MANT-binding pocket suggests that residues outside of the binding site influence isoform selectivity toward MANT-GTP.
About this StructureAbout this Structure
1TL7 is a Protein complex structure of sequences from Bos taurus, Canis lupus familiaris and Rattus norvegicus. Full crystallographic information is available from OCA.
ReferenceReference
Structural basis for the inhibition of mammalian membrane adenylyl cyclase by 2 '(3')-O-(N-Methylanthraniloyl)-guanosine 5 '-triphosphate., Mou TC, Gille A, Fancy DA, Seifert R, Sprang SR, J Biol Chem. 2005 Feb 25;280(8):7253-61. Epub 2004 Dec 9. PMID:15591060
Page seeded by OCA on Thu Mar 20 14:19:49 2008