𝔖 Bobbio Scriptorium
✦   LIBER   ✦

Cyclophilin: a specific cytosolic binding protein for cyclosporin A

✍ Scribed by Handschumacher, R.; Harding, M.; Rice, J; Drugge, R.; Speicher, D.


Book ID
111679023
Publisher
American Association for the Advancement of Science
Year
1984
Tongue
English
Weight
1002 KB
Volume
226
Category
Article
ISSN
0036-8075

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✦ Synopsis


Mbar a linear extrapolation (dasheine) to a maxumum loading force of 7000 N produced a central pressure of 2.8 Mbar. This method is similar but superior to conventional methods of ultrahigh-pressure calibration because it in- corporates supporting data at radial dis- tances.

In the second method the maximum pressure was determined from the pres- sure distribution by calculation of the ratio of the pressure at a radial distance of 30 p.m to the pressure at the center of the flat region. An important factor associated with using the ratio in these calcu- lations is that the flat diamond surface did not undergo plastic deformation. This ratio was constant for anvil set 2 at several central pressures up to 1.8 Mbar (Fig. 2b). The resulting maximum pres- sure in the central area of anvil set 2 was thus determined independently of the loading force to be 2.8 Mbar when pres- sure at the 30-p.m radius was 1.8 Mbar.

The design of anvil set 2 was found to have exceptional properties. Pressure could be raised smoothly to above 2 Mbar after alignment procedures. The conditions were unusually stable; the pressure in the sample region did not vary perceptibly during the 40 day peri- od of the experiment. Unloading the pressure slowly did not produce as fa- vorable stress distributions as loading the pressure, but the diamond anvils were reclaimed after the experiment. These results with a composite of stainless steel and ruby crystals suggest that it should be possible to pressurize any other gasketed materials stably for study at 2 to 3 Mbar with this apparatus, including solids normally in the gaseous state at I bar such as hydrogen.


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Human cyclophilin A (hCypA) contains one tryptophan residue at position 121 (Trp121). The fluorescence intensity of this single tryptophan residue doubles upon binding the clinically important immunosuppressant cyclosporin A (CsA). Trp121 is in close contact to the bound CsA and is well-conserved in