1d7l
From Proteopedia
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'''STRUCTURE-FUNCTION CORRELATIONS OF THE REACTION OF REDUCED NICOTINAMIDE ANALOGS WITH P-HYDROXYBENZOATE HYDROXYLASE SUBSTITUTED WITH A SERIES OF 8-SUBSTITUTED FLAVINS''' | '''STRUCTURE-FUNCTION CORRELATIONS OF THE REACTION OF REDUCED NICOTINAMIDE ANALOGS WITH P-HYDROXYBENZOATE HYDROXYLASE SUBSTITUTED WITH A SERIES OF 8-SUBSTITUTED FLAVINS''' | ||
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[[Category: Massey, V.]] | [[Category: Massey, V.]] | ||
[[Category: Ortiz-Maldonado, M.]] | [[Category: Ortiz-Maldonado, M.]] | ||
| - | [[Category: | + | [[Category: Flavin]] |
| - | [[Category: | + | [[Category: Phbh]] |
| - | [[Category: | + | [[Category: Substituted flavin]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 13:32:09 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 10:32, 2 May 2008
STRUCTURE-FUNCTION CORRELATIONS OF THE REACTION OF REDUCED NICOTINAMIDE ANALOGS WITH P-HYDROXYBENZOATE HYDROXYLASE SUBSTITUTED WITH A SERIES OF 8-SUBSTITUTED FLAVINS
Overview
Structural and kinetic studies have revealed two flavin conformations in p-hydroxybenzoate hydroxylase (PHBH), the in-position and the out-position. Conversion between these two conformations is believed to be essential during catalysis. Although substrate hydroxylation occurs while the flavin in PHBH is in the in-conformation, the position of the flavin during reduction by NADPH is uncertain. To investigate the catalytic importance of the out-conformation of the flavin and to clarify the mechanism of flavin reduction in PHBH, we report quantitative structure-reactivity relationships (QSAR) using PHBH substituted separately with nine derivatives of FAD modified in the 8-position and four dihydronicotinamide analogues as reducing agents. The 8-position of the FAD isoalloxazine ring was chosen for modification because in PHBH it has minimal interactions with the protein and is accessible to solvent. The chemical sequence of events during catalysis by PHBH was not altered when using any of the modified flavins, and normal products were obtained. Although the rate of reduction of PHBH reconstituted with flavin derivatives is expected to be dependent on the redox potential of the flavin, no strict correlation was observed. Instead, the rate of reduction correlated with the kappa-substituent constant, which is based on size and hydrophobicity of the 8-substituent on the FAD. Substituents that sterically hinder attainment of the out-conformation decreased the rate of flavin reduction much more than expected on the basis of the redox potential of the flavin. The results of this QSAR analysis are consistent with the hypothesis that the flavin in PHBH must move to the out-conformation for proper formation of the charge-transfer complex between NADPH and FAD that is necessary for rapid flavin reduction.
About this Structure
1D7L is a Single protein structure of sequence from Pseudomonas aeruginosa. Full crystallographic information is available from OCA.
Reference
Structure-function correlations of the reaction of reduced nicotinamide analogues with p-hydroxybenzoate hydroxylase substituted with a series of 8-substituted flavins., Ortiz-Maldonado M, Gatti D, Ballou DP, Massey V, Biochemistry. 1999 Dec 14;38(50):16636-47. PMID:10600126 Page seeded by OCA on Fri May 2 13:32:09 2008
