Literature summary for 1.3.1.91 extracted from

Whelan, F.; Jenkins, H.T.; Griffiths, S.C.; Byrne, R.T.; Dodson, E.J.; Antson, A.A.
From bacterial to human dihydrouridine synthase automated structure determination (2015), Acta Crystallogr. Sect. D, 71, 1564-1571 .

Application

Application	Comment	Organism
diagnostics	the enzyme defined as an independent prognostic factor for the development of non-small cell lung cancer cells	Homo sapiens
medicine	the enzyme may serve as a valuable target for therapeutic intervention in pulmonary carcinogenesis	Homo sapiens

Cloned(Commentary)

Cloned (Comment)	Organism
recombinant expression of wild-type and selenomethionine-labeled hDus2 1-340 fragment, comprising the hDus2 catalytic and tRNA-recognition domains, in Escherichia coli strains BL21(DE3) and B834(DE3), respectively	Homo sapiens

Crystallization (Commentary)

Crystallization (Comment)	Organism
purified recombinant hDus2 catalytic and tRNA-recognition domains (residues 1-340), sitting drop vapour diffusion method, 300 nl of 10 mg/ml protein in 20 mM Tris, pH 8.0, 100 mM NaCl, 5 mM imidazole, and 5 mM DTT, are mixed with 0. 54 ml of reservoir solution containing 0.1 M MES-malic acid-Tris, pH 4.0, and 25% w/v PEG 1500, 2 days, 19°C, X-ray diffraction structure determination and analysis by single-wavelength anomalous diffraction at 1.9 A resolution, automated molecular replacement with different search models, and modeling	Homo sapiens

Crystallization (Comment)

Organism

purified recombinant hDus2 catalytic and tRNA-recognition domains (residues 1-340), sitting drop vapour diffusion method, 300 nl of 10 mg/ml protein in 20 mM Tris, pH 8.0, 100 mM NaCl, 5 mM imidazole, and 5 mM DTT, are mixed with 0. 54 ml of reservoir solution containing 0.1 M MES-malic acid-Tris, pH 4.0, and 25% w/v PEG 1500, 2 days, 19°C, X-ray diffraction structure determination and analysis by single-wavelength anomalous diffraction at 1.9 A resolution, automated molecular replacement with different search models, and modeling

Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
additional information	siRNA-dependent knockdown of hDus2 decreases colony formation and cell viability of non-small cell lung cancer cells, while hDus2 immunohistochemical staining correlated with patient survival	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
uracil20 in tRNA + NAD(P)H + H+	Homo sapiens	-	5,6-dihydrouracil20 in tRNA + NAD(P)+	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q9NX74	-	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant wild-type and selenomethionine-labeled hDus2 1-340 fragment, comprising the hDus2 catalytic and tRNA-recognition domains, from Escherichia coli strains BL21(DE3) and B834(DE3), respectively	Homo sapiens

Source Tissue

Source Tissue	Comment	Organism	Textmining
non-small cell lung cancer cell	elevated hDus2 mRNA and protein levels	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
uracil20 in tRNA + NAD(P)H + H+	-	Homo sapiens	5,6-dihydrouracil20 in tRNA + NAD(P)+	-	?

Subunits

Subunits	Comment	Organism
More	three-dimensional structure analysis of wild-type and selenomethionine-labeled hDus2 catalytic and tRNA-recognition domains, and modeling, overview	Homo sapiens

Synonyms

Synonyms	Comment	Organism
dihydrouridine synthase	-	Homo sapiens
dihydrouridine synthase 2	-	Homo sapiens
Dus	-	Homo sapiens
hDUS2	-	Homo sapiens

Cofactor

Cofactor	Comment	Organism	Structure
NAD(P)H	-	Homo sapiens

General Information

General Information	Comment	Organism
evolution	In humans, there are four Dus enzymes. The hDus2 subfamily is proposed to specifically modify U20. The overall fold of the human Dus2 is similar to that of bacterial enzymes, but has a larger recognition domain and a unique three-stranded antiparallel beta-sheet insertion into the catalytic domain that packs next to the recognition domain, contributing to domain-domain interactions	Homo sapiens
malfunction	increased expression of human dihydrouridine synthase 2 (hDus2) is linked to pulmonary carcinogenesis, while its knockdown decreases cancer cell line viability	Homo sapiens
additional information	tRNA binding and the active site structure, overview	Homo sapiens
physiological function	dihydrouridine is produced by dihydrouridine synthase (Dus) by enzymatic reduction of the C5-C6 bond in uridine	Homo sapiens