Disease relevance of C00779

• From these samples, the stereochemical preference for hydrogen abstraction during the dehydration reaction mediated by the enzyme scytalone dehydratase was determined [1].

High impact information on C00779

• We introduced four key catalytic residues into NTF2 to create a scytalone dehydratase-like active site [2].
• Structural similarities between the enzyme scytalone dehydratase with nuclear transport factor 2 (NTF2) suggested the potential for NTF2 to be re-engineered into a scytalone dehydratase-like enzyme [2].
• The NTF2 polypeptide chain forms an alpha + beta barrel that opens at one end to form a distinctive hydrophobic cavity and its fold is homologous to that of scytalone dehydratase [3].
• Theoretical calculations indicate that such distortions are more readily achieved in the substrate 2,3-dihydro-2,5-dihydroxy-4H-benzopyran-4-one (DDBO) than in the physiological substrates vermelone and scytalone by approximately 2 kcal/mol [4].
• Melanized conidia of the wild type and the scytalone-treated albino were also more resistant to phagocytosis and killing by human monocytes and murine macrophages than were unmelanized conidia of the two mutants [5].

Biological context of C00779

• Relative substrate specificities for the two physiological substrates, scytalone and veremelone, versus a Ser129 mutant help assign the orientation of the substrates within the active site [6].
• The deduced amino acid sequence of the N-terminal region of SCD1 showed high similarity to the amino acid sequence of scytalone dehydratase from Cochliobolus miyabeanus [7].
• We here propose that LinA is a member of a novel structural superfamily of proteins containing scytalone dehydratase, 3-oxo-Delta(5)-steroid isomerase, nuclear transport factor 2, and the beta-subunit of naphthalene dioxygenase-all known structures with different functions [8].
• A plasmid containing the SCD1 gene transformed the melanin-deficient mutant 9201Y (Scd-) to the wild phenotype but did not complement the conditional scytalone dehydratase-deficient mutant C. lagenarium 8015 [7].
• PKS1 null mutants had an albino phenotype, and pigmentation was restored by the addition of scytalone, a melanin pathway intermediate [9].

Anatomical context of C00779

• Transmission electron microscopy showed an electron-dense granular material believed to be melanin in wild-type conidial cell walls, and this was absent in conidial walls of the albino mutant unless the albino was grown on a scytalone-amended medium [5].

Associations of C00779 with other chemical compounds

• A survey of 12 active-site amino acid residues reveals 4 site-directed mutants (H110N, N131A, F53A, and F53L) have higher relative values of k(cat) and k(cat)/K(m) for DDBO over scytalone and for DDBO over vermelone than the wild-type enzyme, thus suggesting substrate-distortion roles for the native residues in catalysis [4].
• Cryogenic X-ray crystal structure analysis for the complex of scytalone dehydratase of a rice blast fungus and its tight-binding inhibitor, carpropamid: the structural basis of tight-binding inhibition [10].
• The syn elimination is compatible with the interactions realized between a scytalone boat conformation and key active site residues as modeled from multiple X-ray crystal structures of the enzyme in complexes with inhibitors [1].
• Among the active-site residues of scytalone dehydratase, the side-chain carboxamide of asparagine 131 has the greatest potential for strong electrostatic interactions [11].
• The first reduction to produce scytalone was studied in a biomimetic reduction with sodium borohydride [12].

Gene context of C00779

• On the basis of the X-ray crystal structure of scytalone dehydratase complexed with an active center inhibitor [Lundqvist, T., Rice, J., Hodge, C. N., Basarab, G. S., Pierce, J. and Lindqvist, Y. (1994) Structure (London) 2, 937-944], eight active-site residues were mutated to examine their roles in the catalytic mechanism [6].
• The disruption of PKS1 and restoration of pigmentation with scytalone confirmed the presence of a dihydroxynaphthalene-melanin pathway in C. resinifera [9].
• We isolated and characterized SCD1, a gene encoding scytalone dehydratase, from the phytopathogenic fungus Bipolaris oryzae [13].

Analytical, diagnostic and therapeutic context of C00779

• Crystallization trials of scytalone dehydratase were undertaken with the expectation that structural information on this enzyme would facilitate design of high affinity inhibitors which might find use in the control of rice blast disease [14].
• Sequence analysis showed that SCD1 encodes a putative protein that has 185 amino acids, a molecular weight of 21 kDa and 51-75% sequence identity to other fungal scytalone dehydratases [13].
• Diagnosis of dehydratase inhibitors in melanin biosynthesis inhibitor (MBI-D) resistance by primer-introduced restriction enzyme analysis in scytalone dehydratase gene of Magnaporthe grisea [15].

References