Journal article
Structural basis for high‐affinity volatile anesthetic binding in a natural 4‐helix bundle protein
The FASEB journal, v 19(6), pp 567-576
Apr 2005
PMID: 15791007
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
ABSTRACT
Physiologic sites for inhaled anesthetics are presumed to be cavities within transmembrane 4‐α‐helix bundles of neurotransmitter receptors, but confirmation of binding and structural detail of such sites remains elusive. To provide such detail, we screened soluble proteins containing this structural motif, and found only one that exhibited evidence of strong anesthetic binding. Ferritin is a 24‐mer of 4‐α‐helix bundles; both halothane and isoflurane bind with KA values of ∼105 M−1, higher than any previously reported inhaled anesthetic‐protein interaction. The crystal structures of the halothane/apoferritin and isoflurane/apoferritin complexes were determined at 1.75 Å resolution, revealing a common anesthetic binding pocket within an interhelical dimerization interface. The high affinity is explained by several weak polar contacts and an optimal host/guest packing relationship. Neither the acidic protons nor ether oxygen of the anesthetics contribute to the binding interaction. Compared with unliganded apoferritin, the anesthetic produced no detectable alteration of structure or B factors. The remarkably high affinity of the anesthetic/apoferritin complex implies greater selectivity of protein sites than previously thought, and suggests that direct protein actions may underlie effects at lower than surgical levels of anesthetic, including loss of awareness.—Liu, R., Loll, P. J. Eckenhoff, R. G. Structural basis for high‐affinity volatile anesthetic binding in a natural 4‐helix bundle protein. FASEB J. 19, 567–576 (2005)
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Details
- Title
- Structural basis for high‐affinity volatile anesthetic binding in a natural 4‐helix bundle protein
- Creators
- Renyu Liu - University of PennsylvaniaPatrick J Loll - Drexel University College of MedicineRoderic G Eckenhoff - University of Pennsylvania
- Publication Details
- The FASEB journal, v 19(6), pp 567-576
- Publisher
- Wiley
- Number of pages
- 10
- Grant note
- NIGMS (P-01 55876) Fanny Ripple Foundation National Center for Research Resources Biological and Environmental Research
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000228865300041
- Scopus ID
- 2-s2.0-16344374288
- Other Identifier
- 991014878122004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Biology
- Cell Biology