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| STRUCTURE AND DYNAMICS OF THE ACTIVE-SITE GORGE OF ACETYLCHOLINESTERASE - SYNERGISTIC USE OF MOLECULAR-DYNAMICS SIMULATION AND X-RAY CRYSTALLOGRAPHY |
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| Author(s): AXELSEN PH, HAREL M, SILMAN I, SUSSMAN JL |
| Source: PROTEIN SCIENCE Volume: 3 Issue: 2 Pages: 188-197 Published: FEB 1994 |
| Times Cited: 100 References: 32 |
| Abstract: The active site of acetylcholinesterase (AChE) from Torpedo californica is located 20 Angstrom from the enzyme surface at the bottom of a narrow gorge. To understand the role of this gorge in the function of AChE, we have studied simulations of its molecular dynamics. When simulations were conducted with pure water filling the gorge, residues in the vicinity of the active site deviated quickly and markedly from the crystal structure; Further study of the original crystallographic data suggests that a bis-quaternary decamethonium (DECA) ion, acquired during enzyme purification, resides in the gorge. There is additional electron density within the gorge that may represent small bound cations. When DECA and 2 cations are placed within the gorge, the simulation and the crystal structure are dramatically reconciled. The small cations, more so than DECA, appear to stabilize part of the gorge wall through electrostatic interactions. This part of the gorge wall is relatively thin and may regulate substrate, product, and water movement through the active site. |
| Document Type: Article |
| Language: English |
| Reprint Address: AXELSEN, PH (reprint author), UNIV PENN, DEPT PHARMACOL, PHILADELPHIA, PA 19104 USA |
Addresses:
1. WEIZMANN INST SCI, DEPT STRUCT BIOL, IL-76100 REHOVOT, ISRAEL
2. WEIZMANN INST SCI, DEPT NEUROBIOL, IL-76100 REHOVOT, ISRAEL |
| Publisher: CAMBRIDGE UNIV PRESS, 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: MZ675 |
| ISSN: 0961-8368 |
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