ML-I is an enzyme that has the ability to inactivate ribosomes and inhibit cell replication. It is a
target for new cancer treatments. Crystals of the protein attached to adenine (2 of 5 building
blocks of DNA or RNA) were flown, and these crystals yielded X-ray data to 1.9 angstrom. These
data were used to refine the structure of the complex and were especially valuable in refining
the active site conformation (Krauspenhaar 2002). Perhaps the most exciting results from the
macromolecular crystallization experiments conducted in the CPCG-H hardware were obtained
from the Thermus flavus 5S rRNA [ribosomal ribonucleic acid] experiments. These experiments
involved a synthetic RNA duplex of 5S rRNA, which is a model system for the study of the
binding of ribosomal RNA to proteins. Crystallization under microgravity provided crystals of
significantly higher quality than those grown in one-g. The space crystals diffracted to a
maximum resolution of 2.6 angstrom in contrast to the best Earth-grown crystals, which
diffracted to 2.9 angstrom. The improved X-ray data facilitated the completion of the structure
of the RNA segment (Vallazza 2002).
To understand the true function of a protein, the structure must be determined. The model of
the structure must be accurate to allow scientists to create compounds that bind to the
protein. The understanding of the protein structure is of major importance with complex
proteins (proteins that have significant folding). The 3-D structure of the triple mutant protein
Mb-YQR was solved by growing the protein on ISS during Expeditions 2 and 4. Following return
to Earth, 3-D models were created of the Mb-YQR proteins grown in space using X-ray
crystallography techniques (Miele 2004).
Structural studies of microgravity-grown crystals have provided important information for the
development of new drugs. For example, previous studies conducted using crystals grown on
shuttle flights have been used in the design of inhibitors, which may serve as broad-spectrum
antibiotics. The CPCG-H payload offers a great increase in the amount of space available for
protein crystal growth, enhancing the space station’s research capabilities and commercial
potential.
PUBLICATION(S)
Miele AE, Federici L, Sciara G, Draghi F, Brunori M, Vallone B. Analysis of the effect of
microgavity on protein crystal quality: The case of a myoglobin triple mutant. Acta
Crystallographica Section D: Biological Crystallography. 2004;D59: 928-988.
Krauspenhaar R, Rypniewski W, Kalkura N, et al. Crystallisation under microgravity of mistletoe
lectin I from Viscum album with adenine monophosphate and the crystal structure at 1.9
angstrom resolution. Acta Crystallographica Section D: Biological Crystallography.
2002;58:1704-1707.
Nardini M, Spano S, Cericola C, et al. Crystallization and preliminary X-ray diffraction analysis of
brefeldin A-ADP ribosylated substrate (BARS). Acta Crystallographica Section D: Biological
Crystallography. 2002;58: 1068-1070.