1hlf
From Proteopedia
(New page: 200px<br /><applet load="1hlf" size="450" color="white" frame="true" align="right" spinBox="true" caption="1hlf, resolution 2.26Å" /> '''BINDING OF GLUCOPYRA...) |
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| - | [[Image:1hlf.gif|left|200px]]<br /><applet load="1hlf" size=" | + | [[Image:1hlf.gif|left|200px]]<br /><applet load="1hlf" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1hlf, resolution 2.26Å" /> | caption="1hlf, resolution 2.26Å" /> | ||
'''BINDING OF GLUCOPYRANOSYLIDENE-SPIRO-THIOHYDANTOIN TO GLYCOGEN PHOSPHORYLASE B: KINETIC AND CRYSTALLOGRAPHIC STUD'''<br /> | '''BINDING OF GLUCOPYRANOSYLIDENE-SPIRO-THIOHYDANTOIN TO GLYCOGEN PHOSPHORYLASE B: KINETIC AND CRYSTALLOGRAPHIC STUD'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Glucopyranosylidene spirothiohydantoin (TH) has been identified as a | + | Glucopyranosylidene spirothiohydantoin (TH) has been identified as a potential inhibitor of both muscle and liver glycogen phosphorylase b (GPb) and a (GPa) and shown to diminish liver GPa activity in vitro. Kinetic experiments reported here show that TH inhibits muscle GPb competitively with respect to both substrates phosphate (K(i)=2.3 microM) and glycogen (K(i)=2.8 microM). The structure of the GPb-TH complex has been determined at a resolution of 2.26 A and refined to a crystallographic R value of 0.193 (R(free)=0.211). The structure of GPb-TH complex reveals that the inhibitor can be accommodated in the catalytic site of T-state GPb with very little change of the tertiary structure, and provides a basis of understanding potency and specificity of the inhibitor. The glucopyranose moiety makes the standard hydrogen bonds and van der Waals contacts as observed in the glucose complex, while the rigid thiohydantoin group is in a favourable electrostatic environment and makes additional polar contacts to the protein. |
==About this Structure== | ==About this Structure== | ||
| - | 1HLF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus] with PLP and GL4 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Phosphorylase Phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.1 2.4.1.1] Full crystallographic information is available from [http:// | + | 1HLF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus] with <scene name='pdbligand=PLP:'>PLP</scene> and <scene name='pdbligand=GL4:'>GL4</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Phosphorylase Phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.1 2.4.1.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HLF OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Docsa, T.]] | [[Category: Docsa, T.]] | ||
[[Category: Gergely, P.]] | [[Category: Gergely, P.]] | ||
| - | [[Category: Oikonomakos, N | + | [[Category: Oikonomakos, N G.]] |
[[Category: Osz, E.]] | [[Category: Osz, E.]] | ||
| - | [[Category: Skamnaki, V | + | [[Category: Skamnaki, V T.]] |
[[Category: Somsak, L.]] | [[Category: Somsak, L.]] | ||
[[Category: Szilagyi, L.]] | [[Category: Szilagyi, L.]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:02:32 2008'' |
Revision as of 11:02, 21 February 2008
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BINDING OF GLUCOPYRANOSYLIDENE-SPIRO-THIOHYDANTOIN TO GLYCOGEN PHOSPHORYLASE B: KINETIC AND CRYSTALLOGRAPHIC STUD
Overview
Glucopyranosylidene spirothiohydantoin (TH) has been identified as a potential inhibitor of both muscle and liver glycogen phosphorylase b (GPb) and a (GPa) and shown to diminish liver GPa activity in vitro. Kinetic experiments reported here show that TH inhibits muscle GPb competitively with respect to both substrates phosphate (K(i)=2.3 microM) and glycogen (K(i)=2.8 microM). The structure of the GPb-TH complex has been determined at a resolution of 2.26 A and refined to a crystallographic R value of 0.193 (R(free)=0.211). The structure of GPb-TH complex reveals that the inhibitor can be accommodated in the catalytic site of T-state GPb with very little change of the tertiary structure, and provides a basis of understanding potency and specificity of the inhibitor. The glucopyranose moiety makes the standard hydrogen bonds and van der Waals contacts as observed in the glucose complex, while the rigid thiohydantoin group is in a favourable electrostatic environment and makes additional polar contacts to the protein.
About this Structure
1HLF is a Single protein structure of sequence from Oryctolagus cuniculus with and as ligands. Active as Phosphorylase, with EC number 2.4.1.1 Full crystallographic information is available from OCA.
Reference
Kinetic and crystallographic studies of glucopyranosylidene spirothiohydantoin binding to glycogen phosphorylase B., Oikonomakos NG, Skamnaki VT, Osz E, Szilagyi L, Somsak L, Docsa T, Toth B, Gergely P, Bioorg Med Chem. 2002 Feb;10(2):261-8. PMID:11741774
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