Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A female patient, the first child of healthy non-consanguineous parents, presented at the age of 16 months with delayed motor development and facial dysmorphism. In addition she displayed a palatoschizis and multiple skeletal abnormalities as hypoplastic scapulae, hypoplastic os ilea, and an extreme cervical kyphosis. Biochemical investigation of urine revealed no abnormalities except for the presence of large amounts of reducing sugars. The sugar was identified as L-arabinose, which mainly originated from fruit formula in her diet. In addition highly elevated levels of L-arabitol were found in urine, plasma, and cerebrospinal fluid. Although little is known about human arabinose metabolism, we presume that L-arabitol dehydrogenase is deficient in our patient. As polyols are potentially toxic to the central nervous system there could be deleterious long-term effects of this disorder. Withdrawal of dietary fruit led to normalization of polyol levels. The above-mentioned clinical abnormalities are probably not related to this new inborn error of metabolism and should be considered as a separate entity.
Mol Genet Metab
PMID:L-Arabinosuria: a new defect in human pentose metabolism. 1235 33

L-arabinitol 4-dehydrogenase (LAD1; EC 1.1.1.12) is an enzyme in the L-arabinose catabolic pathway of fungi that catalyzes the conversion of L-arabinitol into L-xylulose. The primary objective of this work is to identify the catalytic and coenzyme binding domains of LAD1 from Hypocrea jecorina in order to provide better insight into the possible catalytic events in these domains. The 3D structure of NAD(+)-dependent LAD1 was developed based on the crystal structure of human sorbitol dehydrogenase as a template. A series of molecular mechanics and dynamics operations were performed to find the most stable binding interaction for the enzyme and its ligands. Using the verified model, a docking study was performed with the substrate L-arabinitol, Zn(2+) and NAD(+). This study found a catalytic Zn(2+) binding domain (Cys66, His91, Glu92 and Glu176) and a cofactor NAD(+) binding domain (Gly202, ILeu204, Gly205, Cys273, Arg229 and Val298) with strong hydrogen bonding contacts with the substrate and cofactor. The binding pockets of the enzyme for l-arabinitol, NAD(+), and Zn(2+) have been explicitly defined. The results from this study should guide future mutagenesis studies and provide useful clues for engineering enzymes to improve the utilization of polyols for rare sugar production.
J Mol Graph Model 2010 Jun
PMID:Molecular modeling studies of L-arabinitol 4-dehydrogenase of Hypocrea jecorina: its binding interactions with substrate and cofactor. 2017 13

L-arabinitol 4-dehydrogenase (LAD) catalyzes the conversion of l-arabinitol into l-xylulose with concomitant NAD(+) reduction. It is an essential enzyme in the development of recombinant organisms that convert l-arabinose into fuels and chemicals using the fungal l-arabinose catabolic pathway. Here we report the crystal structure of LAD from the filamentous fungus Neurospora crassa at 2.6 A resolution. In addition, we created a number of site-directed variants of N. crassa LAD that are capable of utilizing NADP(+) as cofactor, yielding the first example of LAD with an almost completely switched cofactor specificity. This work represents the first structural data on any LAD and provides a molecular basis for understanding the existing literature on the substrate specificity and cofactor specificity of this enzyme. The engineered LAD mutants with altered cofactor specificity should be useful for applications in industrial biotechnology.
J Mol Biol 2010 Sep 10
PMID:Structure and engineering of L-arabinitol 4-dehydrogenase from Neurospora crassa. 2065 16