TAILIEUCHUNG - Báo cáo khoa học: Medium-chain dehydrogenases/reductases (MDR) Family characterizations including genome comparisons and active site modelling

Completed eukaryotic genomes were screened for medium-chain dehydrogenases/reductases (MDR). In the human genome, 23 MDR forms were found, a number that prob-ably will increase, because the genome is not yet fully inter-preted. Partial sequences already indicate that at least three furthermembers , at least eight families were distinguished. | Eur. J. Biochem. 269 4267-4276 2002 FEBS 2002 doi Medium-chain dehydrogenases reductases MDR Family characterizations including genome comparisons and active site modelling Erik Nordling1 2 Hans Jornvall1 and Bengt Persson1 2 1 Department of Medical Biochemistry and Biophysics and 2Stockholm Bioinformatics Centre Karolinska Institutet Stockholm Sweden Completed eukaryotic genomes were screened for mediumchain dehydrogenases reductases MDR . In the human genome 23 MDR forms were found a number that probably will increase because the genome is not yet fully interpreted. Partial sequences already indicate that at least three further members exist. Within the MDR superfamily at least eight families were distinguished. Three families are formed by dimeric alcohol dehydrogenases ADH originally detected in animals plants cinnamyl alcohol dehydrogenases originally detected in plants and tetrameric alcohol dehydrogenases originally detected in yeast . Three further families are centred around forms initially detected as mitochondrial respiratory function proteins acetyl-CoA reductases of fatty acid synthases and leukotriene B4 dehydrogenases. The two remaining families with polyol dehydrogenases originally detected as sorbitol dehydrogenase and quinone reductases originally detected as f-crystallin are also distinct but with variable sequences. The most abundant families in the human genome are the dimeric ADH forms and the quinone oxidoreductases. The eukaryotic patterns are different from those of Escherichia coli. The different families were further evaluated by molecular modelling of their active sites as to geometry hydrophobicity and volume of substrate-binding pockets. Finally sequence patterns were derived that are diagnostic for the different families and can be used in genome annotations. Keywords medium-chain dehydrogenases reductases genome comparisons polyol dehydrogenase cinnamyl alcohol dehydrogenase quinone oxidoreductase. .

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