Comparison of AMP and NADH binding to glycogen phosphorylase b.
The binding sites for the allosteric activator, AMP, to glycogen phosphorylase b are described in detail utilizing the more precise knowledge of the native structure obtained from crystallographic restrained least-squares refinement than has hitherto been available. Localized conformational changes...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
1983
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| _version_ | 1797075132823371776 |
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| author | Stura, E Zanotti, G Babu, Y Sansom, MS Stuart, D Wilson, K Johnson, L Van de Werve, G |
| author_facet | Stura, E Zanotti, G Babu, Y Sansom, MS Stuart, D Wilson, K Johnson, L Van de Werve, G |
| author_sort | Stura, E |
| collection | OXFORD |
| description | The binding sites for the allosteric activator, AMP, to glycogen phosphorylase b are described in detail utilizing the more precise knowledge of the native structure obtained from crystallographic restrained least-squares refinement than has hitherto been available. Localized conformational changes are seen at the allosteric effector site that include shifts of between 1 and 2 A for residues Tyr75 and Arg309 and very small shifts for the region of residues 42 to 44 from the symmetry-related subunit. Kinetic studies demonstrate that NADH inhibits the AMP activation of glycogen phosphorylase b. Crystallographic binding studies at 3.5 A resolution show that NADH binds to the same sites on the enzyme as AMP, i.e. the allosteric effector site N, which is close to the subunit-subunit interface, and the nucleoside inhibitor site I, which is some 12 A from the catalytic site. The conformations of NADH at the two sites are different but both conformations are "folded" so that the nicotinamide ring is close (approx. 6 A) to the adenine ring. These conformations are compared with those suggested from solution studies and with the extended conformations observed in the single crystal structure of NAD+ and for NAD bound to dehydrogenases. Possible mechanisms for NADH inhibition of phosphorylase activation are discussed. |
| first_indexed | 2024-03-06T23:46:00Z |
| format | Journal article |
| id | oxford-uuid:70e98a67-d887-4cc8-98c7-120b007fdb53 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:46:00Z |
| publishDate | 1983 |
| record_format | dspace |
| spelling | oxford-uuid:70e98a67-d887-4cc8-98c7-120b007fdb532022-03-26T19:40:24ZComparison of AMP and NADH binding to glycogen phosphorylase b.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:70e98a67-d887-4cc8-98c7-120b007fdb53EnglishSymplectic Elements at Oxford1983Stura, EZanotti, GBabu, YSansom, MSStuart, DWilson, KJohnson, LVan de Werve, GThe binding sites for the allosteric activator, AMP, to glycogen phosphorylase b are described in detail utilizing the more precise knowledge of the native structure obtained from crystallographic restrained least-squares refinement than has hitherto been available. Localized conformational changes are seen at the allosteric effector site that include shifts of between 1 and 2 A for residues Tyr75 and Arg309 and very small shifts for the region of residues 42 to 44 from the symmetry-related subunit. Kinetic studies demonstrate that NADH inhibits the AMP activation of glycogen phosphorylase b. Crystallographic binding studies at 3.5 A resolution show that NADH binds to the same sites on the enzyme as AMP, i.e. the allosteric effector site N, which is close to the subunit-subunit interface, and the nucleoside inhibitor site I, which is some 12 A from the catalytic site. The conformations of NADH at the two sites are different but both conformations are "folded" so that the nicotinamide ring is close (approx. 6 A) to the adenine ring. These conformations are compared with those suggested from solution studies and with the extended conformations observed in the single crystal structure of NAD+ and for NAD bound to dehydrogenases. Possible mechanisms for NADH inhibition of phosphorylase activation are discussed. |
| spellingShingle | Stura, E Zanotti, G Babu, Y Sansom, MS Stuart, D Wilson, K Johnson, L Van de Werve, G Comparison of AMP and NADH binding to glycogen phosphorylase b. |
| title | Comparison of AMP and NADH binding to glycogen phosphorylase b. |
| title_full | Comparison of AMP and NADH binding to glycogen phosphorylase b. |
| title_fullStr | Comparison of AMP and NADH binding to glycogen phosphorylase b. |
| title_full_unstemmed | Comparison of AMP and NADH binding to glycogen phosphorylase b. |
| title_short | Comparison of AMP and NADH binding to glycogen phosphorylase b. |
| title_sort | comparison of amp and nadh binding to glycogen phosphorylase b |
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