High-quality crystals of human haematopoietic prostaglandin D synthase with novel inhibitors

Takahashi, Sachiko; Tsurumura, Toshiharu; Aritake, Kosuke; Furubayashi, Naoki; Satô, Masaru; Yamanaka, Masao; Hirota, Erika; Сано, С.; Kobayashi, Tomoyuki; Tanaka, Tetsuo; Inaka, Koji; Tanaka, Hiroaki; Urade, Yoshihiro

doi:10.1107/s1744309110020828

Cited by 54 publications

(37 citation statements)

References 31 publications

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“…Crystals of AlDHPyr1147 as isolated (Holo-1) were grown by the modified capillary counterdiffusion technique [27, 28] in microgravity within six weeks. Crystals of the apo form of AlDHPyr1147 (apo), the complex with NADP+ (Holo-2), and the ternary complex with NADP+ and the substrate were obtained by the hanging-drop vapor-diffusion method in Linbro plates (Hampton Research) at 20°C.…”

Section: Methodsmentioning

confidence: 99%

NADP-Dependent Aldehyde Dehydrogenase from ArchaeonPyrobaculum sp.1860: Structural and Functional Features

Bezsudnova

Petrova

Artemova

et al. 2016

Archaea

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We present the functional and structural characterization of the first archaeal thermostable NADP-dependent aldehyde dehydrogenase AlDHPyr1147. In vitro, AlDHPyr1147 catalyzes the irreversible oxidation of short aliphatic aldehydes at 60–85°С, and the affinity of AlDHPyr1147 to the NADP+ at 60°С is comparable to that for mesophilic analogues at 25°С. We determined the structures of the apo form of AlDHPyr1147 (3.04 Å resolution), three binary complexes with the coenzyme (1.90, 2.06, and 2.19 Å), and the ternary complex with the coenzyme and isobutyraldehyde as a substrate (2.66 Å). The nicotinamide moiety of the coenzyme is disordered in two binary complexes, while it is ordered in the ternary complex, as well as in the binary complex obtained after additional soaking with the substrate. AlDHPyr1147 structures demonstrate the strengthening of the dimeric contact (as compared with the analogues) and the concerted conformational flexibility of catalytic Cys287 and Glu253, as well as Leu254 and the nicotinamide moiety of the coenzyme. A comparison of the active sites of AlDHPyr1147 and dehydrogenases characterized earlier suggests that proton relay systems, which were previously proposed for dehydrogenases of this family, are blocked in AlDHPyr1147, and the proton release in the latter can occur through the substrate channel.

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Section: Methodsmentioning

confidence: 99%

NADP-Dependent Aldehyde Dehydrogenase from ArchaeonPyrobaculum sp.1860: Structural and Functional Features

Bezsudnova

Petrova

Artemova

et al. 2016

Archaea

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“…However, in the cases of H-PGDS complexes with more potent inhibitors, neither penetration of the inhibitor molecule into the ceiling of the catalytic cleft nor pushing out of the indole ring of Trp-104 is observed. 192,193 …”

Section: Prostaglandin D Synthases (Pgdss)mentioning

confidence: 99%

“…179 These results indicate that HQL-79 binds to the PGH 2 -binding site but not to the GSH-binding site, subsequently confirmed by the X-ray crystallographic analysis (Figure 16). The development of novel H-PGDS inhibitors, such as TFC-007 (Figure 19B), with increased selectivity and inhibitory potency is currently being extensively pursued 192,193,205,206 based on crystal structures of the H-PGDS/HQL-79 complex.…”

Section: Prostaglandin D Synthases (Pgdss)mentioning

confidence: 99%

Enzymes of the Cyclooxygenase Pathways of Prostanoid Biosynthesis

2011

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“…The growth of high-quality single crystals of proteins has been intensively pursued using magnetic fields [3][4][5][6][7][8][9], microgravity [10][11][12][13][14][15][16], solution flow [17][18][19][20], and gel as a growth host media [21][22][23][24][25][26][27][28]. A growth technique mediated by screw dislocations under low supersaturation has also been proposed [29][30][31][32].…”

Section: Introductionmentioning

confidence: 99%

Effect of an External Electric Field on the Kinetics of Dislocation-Free Growth of Tetragonal Hen Egg White Lysozyme Crystals

et al. 2017

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Dislocation-free tetragonal hen egg white (HEW) lysozyme crystals were grown from a seed crystal in a cell. The rates of tetragonal HEW lysozyme crystal growth normal to the (110) and (101) faces with and without a 1-MHz external electric field were measured. A decrease in the typical growth rates of the crystal measured under an applied field at 1 MHz was observed, although the overall driving force increased. Assuming that the birth and spread mechanism of two-dimensional nucleation occurs, an increase in the effective surface energy of the step ends was realized in the presence of the electric field, which led to an improvement in the crystal quality of the tetragonal HEW lysozyme crystals. This article also discusses the increase in the effective surface energy of the step ends with respect to the change in the entropy of the solid.

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High-quality crystals of human haematopoietic prostaglandin D synthase with novel inhibitors

Cited by 54 publications

References 31 publications

NADP-Dependent Aldehyde Dehydrogenase from ArchaeonPyrobaculum sp.1860: Structural and Functional Features

NADP-Dependent Aldehyde Dehydrogenase from ArchaeonPyrobaculum sp.1860: Structural and Functional Features

Enzymes of the Cyclooxygenase Pathways of Prostanoid Biosynthesis

Effect of an External Electric Field on the Kinetics of Dislocation-Free Growth of Tetragonal Hen Egg White Lysozyme Crystals

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