Broad Substrate Specificity of Human Cytochrome P450 46A1 Which Initiates Cholesterol Degradation in the Brain†

Biochemistry ◽  
2003 ◽  
Vol 42 (48) ◽  
pp. 14284-14292 ◽  
Author(s):  
Natalia Mast ◽  
Ryan Norcross ◽  
Ulla Andersson ◽  
Magang Shou ◽  
Kazuo Nakayama ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Substrate Specificity ◽  
Broad Substrate Specificity ◽  
Human Cytochrome ◽  
The Brain

Alternative splicing within the human cytochrome P450 superfamily with an emphasis on the brain: the convolution continues

2006 ◽  
Vol 2 (3) ◽  
pp. 399-418 ◽  
Author(s):  
Cheri M Turman ◽  
Jade M Hatley ◽  
Daniel J Ryder ◽  
Vijayalakshmi Ravindranath ◽  
Henry W Strobel
Keyword(s):  
Cytochrome P450 ◽  
Alternative Splicing ◽  
Human Cytochrome ◽  
The Brain

Prediction of amino acid residues participated in substrate recognition by cytochrome P450 subfamilies with broad substrate specificity

2013 ◽  
Vol 26 (2) ◽  
pp. 86-91 ◽  
Author(s):  
Maria S. Zharkova ◽  
Boris N. Sobolev ◽  
Nina Yu. Oparina ◽  
Alexander V. Veselovsky ◽  
Alexander I. Archakov
Keyword(s):  
Cytochrome P450 ◽  
Amino Acid ◽  
Substrate Specificity ◽  
Substrate Recognition ◽  
Amino Acid Residues ◽  
Broad Substrate Specificity

scholarly journals Substrate specificity and structure of human aminoadipate aminotransferase/kynurenine aminotransferase II

2008 ◽  
Vol 28 (4) ◽  
pp. 205-215 ◽  
Author(s):  
Qian Han ◽  
Tao Cai ◽  
Danilo A. Tagle ◽  
Howard Robinson ◽  
Jianyong Li
Keyword(s):  
Substrate Specificity ◽  
Catalytic Efficiency ◽  
Structural Basis ◽  
Substrate Affinity ◽  
Kinetic Properties ◽  
Amino Group ◽  
Kynurenine Aminotransferase ◽  
Broad Substrate Specificity ◽  
Systematic Assessment ◽  
The Brain

KAT (kynurenine aminotransferase) II is a primary enzyme in the brain for catalysing the transamination of kynurenine to KYNA (kynurenic acid). KYNA is the only known endogenous antagonist of the N-methyl-D-aspartate receptor. The enzyme also catalyses the transamination of aminoadipate to α-oxoadipate; therefore it was initially named AADAT (aminoadipate aminotransferase). As an endotoxin, aminoadipate influences various elements of glutamatergic neurotransmission and kills primary astrocytes in the brain. A number of studies dealing with the biochemical and functional characteristics of this enzyme exist in the literature, but a systematic assessment of KAT II addressing its substrate profile and kinetic properties has not been performed. The present study examines the biochemical and structural characterization of a human KAT II/AADAT. Substrate screening of human KAT II revealed that the enzyme has a very broad substrate specificity, is capable of catalysing the transamination of 16 out of 24 tested amino acids and could utilize all 16 tested α-oxo acids as amino-group acceptors. Kinetic analysis of human KAT II demonstrated its catalytic efficiency for individual amino-group donors and acceptors, providing information as to its preferred substrate affinity. Structural analysis of the human KAT II complex with α-oxoglutaric acid revealed a conformational change of an N-terminal fraction, residues 15–33, that is able to adapt to different substrate sizes, which provides a structural basis for its broad substrate specificity.

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