1xz3
From Proteopedia
(New page: 200px<br /><applet load="1xz3" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xz3, resolution 1.75Å" /> '''Complex of apoferrit...) |
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| - | [[Image:1xz3.gif|left|200px]]<br /><applet load="1xz3" size=" | + | [[Image:1xz3.gif|left|200px]]<br /><applet load="1xz3" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1xz3, resolution 1.75Å" /> | caption="1xz3, resolution 1.75Å" /> | ||
'''Complex of apoferritin with isoflurane'''<br /> | '''Complex of apoferritin with isoflurane'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Physiologic sites for inhaled anesthetics are presumed to be cavities | + | Physiologic sites for inhaled anesthetics are presumed to be cavities within transmembrane 4-alpha-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-alpha-helix bundles; both halothane and isoflurane bind with K(A) values of approximately 10(5) 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 A 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1XZ3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Equus_caballus Equus caballus] with CD and ICF as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1XZ3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Equus_caballus Equus caballus] with <scene name='pdbligand=CD:'>CD</scene> and <scene name='pdbligand=ICF:'>ICF</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XZ3 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Equus caballus]] | [[Category: Equus caballus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Eckenhoff, R | + | [[Category: Eckenhoff, R G.]] |
[[Category: Liu, R.]] | [[Category: Liu, R.]] | ||
| - | [[Category: Loll, P | + | [[Category: Loll, P J.]] |
[[Category: CD]] | [[Category: CD]] | ||
[[Category: ICF]] | [[Category: ICF]] | ||
[[Category: 4-helix bundle]] | [[Category: 4-helix bundle]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:00:08 2008'' |
Revision as of 14:00, 21 February 2008
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Complex of apoferritin with isoflurane
Overview
Physiologic sites for inhaled anesthetics are presumed to be cavities within transmembrane 4-alpha-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-alpha-helix bundles; both halothane and isoflurane bind with K(A) values of approximately 10(5) 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 A 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.
About this Structure
1XZ3 is a Single protein structure of sequence from Equus caballus with and as ligands. Full crystallographic information is available from OCA.
Reference
Structural basis for high-affinity volatile anesthetic binding in a natural 4-helix bundle protein., Liu R, Loll PJ, Eckenhoff RG, FASEB J. 2005 Apr;19(6):567-76. PMID:15791007
Page seeded by OCA on Thu Feb 21 16:00:08 2008
Categories: Equus caballus | Single protein | Eckenhoff, R G. | Liu, R. | Loll, P J. | CD | ICF | 4-helix bundle
