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001     94652
005     20250730163918.0
024 7 _ |a pmid:21383134
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024 7 _ |a pmc:PMC3064382
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024 7 _ |a 1091-6490
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024 7 _ |a 0027-8424
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024 7 _ |a 10.1073/pnas.1016684108
|2 doi
024 7 _ |a WOS:000288712200025
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037 _ _ |a PHPPUBDB-18289
041 _ _ |a eng
082 _ _ |a 000
100 1 _ |a Kachalova, G.
110 1 _ |a DESY
|b Experiments with synchrotron radiation
245 _ _ |a Crystallographic snapshots of the complete reaction cycle of nicotine degradation by an amine oxidase of the monoamine oxidase (MAO) family
260 _ _ |a Washington, DC
|c 2011
|b Academy
300 _ _ |a 4800-4805
336 7 _ |a Journal Article
|0 0
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336 7 _ |a article
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336 7 _ |a Journal Article
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336 7 _ |a ARTICLE
|2 BibTeX
440 _ 0 |a Proc. Nat. Acad. Sci. USA
|0 PERI:(DE-600)1461794-8
|v 108
|y 12
|x 1091-6490
500 _ _ |3 Converted on 2013-05-30 15:04
500 _ _ |3 Converted on 2013-06-21 19:21
520 _ _ |a FAD-linked oxidases constitute a class of enzymes which catalyze dehydrogenation as a fundamental biochemical reaction, followed by reoxidation of reduced flavin. Here, we present high-resolution crystal structures showing the flavoenzyme 6-hydroxy-l-nicotine oxidase in action. This enzyme was trapped during catalytic degradation of the native substrate in a sequence of discrete reaction states corresponding to the substrate-reduced enzyme, a complex of the enzyme with the intermediate enamine product and formation of the final aminoketone product. The inactive d-stereoisomer binds in mirror symmetry with respect to the catalytic axis, revealing absolute stereospecificity of hydrogen transfer to the flavin. The structural data suggest deprotonation of the substrate when bound at the active site, an overall binary complex mechanism and oxidation by direct hydride transfer. The amine nitrogen has a critical role in the dehydrogenation step and may activate carbocation formation at the α-carbon via delocalization from the lone pair to σ* C(α)-H. Enzymatically assisted hydrolysis of the intermediate product occurs at a remote (P site) cavity. Substrate entry and product exit follow different paths. Structural and kinetic data suggest that substrate can also bind to the reduced enzyme, associated with slower reoxidation as compared to the rate of reoxidation of free enzyme. The results are of general relevance for the mechanisms of flavin amine oxidases.
536 _ _ |0 G:(DE-H253)POF2-BW6-20130405
|f POF II
|x 0
|c POF2-54G13
|a DORIS Beamline BW6 (POF2-54G13)
588 _ _ |a Dataset connected to Pubmed
650 _ 7 |a Bacterial Proteins
|0 0
|2 NLM Chemicals
650 _ 7 |a Nicotine
|0 54-11-5
|2 NLM Chemicals
650 _ 7 |a Monoamine Oxidase
|0 EC 1.4.3.4
|2 NLM Chemicals
650 _ 7 |a Oxidoreductases Acting on CH-NH Group Donors
|0 EC 1.5.-
|2 NLM Chemicals
650 _ 7 |a 6-hydroxy-L-nicotine oxidase
|0 EC 1.5.3.5
|2 NLM Chemicals
650 _ 2 |a Arthrobacter: enzymology
|2 MeSH
650 _ 2 |a Bacterial Proteins: chemistry
|2 MeSH
650 _ 2 |a Catalytic Domain
|2 MeSH
650 _ 2 |a Crystallography, X-Ray
|2 MeSH
650 _ 2 |a Kinetics
|2 MeSH
650 _ 2 |a Monoamine Oxidase: chemistry
|2 MeSH
650 _ 2 |a Nicotine: chemistry
|2 MeSH
650 _ 2 |a Oxidation-Reduction
|2 MeSH
650 _ 2 |a Oxidoreductases Acting on CH-NH Group Donors: chemistry
|2 MeSH
650 _ 2 |a Structure-Activity Relationship
|2 MeSH
693 _ _ |a DORIS III
|f DORIS Beamline BW6
|1 EXP:(DE-H253)DORISIII-20150101
|0 EXP:(DE-H253)D-BW6-20150101
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700 1 _ |a Decker, K.
700 1 _ |a Holt, A.
700 1 _ |a Bartunik, H. D.
773 _ _ |a 10.1073/pnas.1016684108
|g Vol. 108, p. 4800-4805
|0 PERI:(DE-600)1461794-8
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|t Proceedings of the National Academy of Sciences of the United States of America
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856 7 _ |2 Pubmed Central
|u http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3064382
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914 1 _ |a (c) National Academy of Sciences
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