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'''CRYSTAL STRUCTURE OF 8-AMINO-7-OXONANOATE SYNTHASE (OR 7-KETO-8AMINIPELARGONATE OR KAPA SYNTHASE) COMPLEXED WITH PLP AND THE PRODUCT 8(S)-AMINO-7-OXONANONOATE (OR KAPA). THE ENZYME OF BIOTIN BIOSYNTHETIC PATHWAY.''' | '''CRYSTAL STRUCTURE OF 8-AMINO-7-OXONANOATE SYNTHASE (OR 7-KETO-8AMINIPELARGONATE OR KAPA SYNTHASE) COMPLEXED WITH PLP AND THE PRODUCT 8(S)-AMINO-7-OXONANONOATE (OR KAPA). THE ENZYME OF BIOTIN BIOSYNTHETIC PATHWAY.''' | ||
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[[Category: Watt, R M.]] | [[Category: Watt, R M.]] | ||
[[Category: Webster, S P.]] | [[Category: Webster, S P.]] | ||
[[Category: | [[Category: Biotin]] | ||
[[Category: | [[Category: Pyridoxal-5'-phosphate]] | ||
[[Category: | [[Category: Transferase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 13:54:35 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 13:54, 2 May 2008
CRYSTAL STRUCTURE OF 8-AMINO-7-OXONANOATE SYNTHASE (OR 7-KETO-8AMINIPELARGONATE OR KAPA SYNTHASE) COMPLEXED WITH PLP AND THE PRODUCT 8(S)-AMINO-7-OXONANONOATE (OR KAPA). THE ENZYME OF BIOTIN BIOSYNTHETIC PATHWAY.
OverviewOverview
8-Amino-7-oxononanoate synthase (also known as 7-keto-8-aminopelargonate synthase, EC 2.3.1.47) is a pyridoxal 5'-phosphate-dependent enzyme which catalyzes the decarboxylative condensation of L-alanine with pimeloyl-CoA in a stereospecific manner to form 8(S)-amino-7-oxononanoate. This is the first committed step in biotin biosynthesis. The mechanism of Escherichia coli AONS has been investigated by spectroscopic, kinetic, and crystallographic techniques. The X-ray structure of the holoenzyme has been refined at a resolution of 1.7 A (R = 18.6%, R(free) = 21. 2%) and shows that the plane of the imine bond of the internal aldimine deviates from the pyridine plane. The structure of the enzyme-product external aldimine complex has been refined at a resolution of 2.0 A (R = 21.2%, R(free) = 27.8%) and shows a rotation of the pyridine ring with respect to that in the internal aldimine, together with a significant conformational change of the C-terminal domain and subtle rearrangement of the active site hydrogen bonding. The first step in the reaction, L-alanine external aldimine formation, is rapid (k(1) = 2 x 10(4) M(-)(1) s(-)(1)). Formation of an external aldimine with D-alanine, which is not a substrate, is significantly slower (k(1) = 125 M(-)(1) s(-)(1)). Binding of D-alanine to AONS is enhanced approximately 2-fold in the presence of pimeloyl-CoA. Significant substrate quinonoid formation only occurs upon addition of pimeloyl-CoA to the preformed L-alanine external aldimine complex and is preceded by a distinct lag phase ( approximately 30 ms) which suggests that binding of the pimeloyl-CoA causes a conformational transition of the enzyme external aldimine complex. This transition, which is inferred by modeling to require a rotation around the Calpha-N bond of the external aldimine complex, promotes abstraction of the Calpha proton by Lys236. These results have been combined to form a detailed mechanistic pathway for AONS catalysis which may be applied to the other members of the alpha-oxoamine synthase subfamily.
About this StructureAbout this Structure
1DJ9 is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.
ReferenceReference
Mechanism of 8-amino-7-oxononanoate synthase: spectroscopic, kinetic, and crystallographic studies., Webster SP, Alexeev D, Campopiano DJ, Watt RM, Alexeeva M, Sawyer L, Baxter RL, Biochemistry. 2000 Jan 25;39(3):516-28. PMID:10642176 Page seeded by OCA on Fri May 2 13:54:35 2008