Caged and clustered structures of endothelin inhibitor BQ123, cyclo(-D-Trp-D-Asp(-)-Pro-D-Val-Leu-)center dot Na+, forming five and six coordination bonds between sodium ions and peptides

Doi, M Asano, A Ishida, T Katsuya, Y Mezaki, Y Sasaki, M Terashima, A Taniguchi, T Hasegawa, H Shiono, M

M. Doi et al., Caged and clustered structures of endothelin inhibitor BQ123, cyclo(-D-Trp-D-Asp(-)-Pro-D-Val-Leu-)center dot Na+, forming five and six coordination bonds between sodium ions and peptides, ACT CRYST D, 57, 2001, pp. 628-634

26

INGLESE

Article

Chemistry & Analysis

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY

0907-4449 → ACNP

57

2001

5

628 - 634

ISI

0907-4449(200105)57:<628:CACSOE>2.0.ZU;2-#

BQ123 is a cyclic pentapeptide and a potent endothelin-1 inhibitor. The cry stal structure of the BQ123 sodium salt was determined as the first example of an endothelin inhibitor. Four independent molecules and many solvent mo lecules were found in the asymmetric unit; the total weight was about 3000 Da. The precise structure including the solvent molecules was determined us ing high-resolution data collected on a synchrotron source. Sodium ions for med unique structures with five and six coordination bonds and their forms were distinguished into three classes. An ion was sandwiched by two BQ123 m olecules. This peptide-sodium (2:1) complex showed a cage-like structure an d octahedral coordination was observed. Sodium ions also formed a cluster c omposed of hydrated water molecules and peptides. Two sodium ions were cont ained in this cluster, making five coordination bonds. Despite having the s ame coordination numbers, these ions were distinguishable by differences in the polyhedra. One was trigonal bipyramidal (having six planes) and the ot her was square pyramidal (having five planes). Both shapes were very simila r to each other, although the synchrotron data clearly revealed slight geom etrical differences.