Improvement in the quality of hematopoietic prostaglandin D synthase crystals in a microgravity environment

Abstract

Human hematopoietic prostaglandin synthase, one of the better therapeutic target enzymes for allergy and inflammation, was crystallized with 22 inhibitors and in three inhibitor-free conditions in microgravity. Most of the space-grown crystals showed better X-ray diffraction patterns than the terrestrially grown ones, indicating the advantage of a microgravity environment on protein crystallization, especially in the case of this protein.

Enzymes of the Cyclooxygenase Pathways of Prostanoid Biosynthesis

“…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 …”

“…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.…”

Numerical model of protein crystal growth in a diffusive field such as the microgravity environment

“…Therefore, we speculate that the outer section of crystals grown in TDM may have better quality because the supersaturation ratios and impurity concentrations are lower in the inner section of the crystals grown in TDM than those of the crystals grown in THM. This may explain the reason why some better quality crystals grew in microgravity (Tanaka et al, 2007(Tanaka et al, , 2011Takahashi et al, 2010). Further examination is required to know the influence of the ASS and AIC on the X-ray diffraction patterns quantitatively.…”

Expanded benefits for humanity from the International Space Station

“…Microgravity allows unique conditions for growth of protein crystals where there is no gravity or convection to disrupt their growth [13]. The protein expressed in certain muscle fibers of patients with Duchenne's Muscular Dystrophy, which affects 1 in 3,500 boys, has been successfully crystallized in space [ Figure 6] revealing a new inhibitor several hundred times stronger than the prototype inhibitor [14].…”