Linked Life Data

20481504

Source:http://linkedlifedata.com/resource/pubmed/id/20481504

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2010-6-15
pubmed:abstractText
Crystal structures of methyl, ethyl, propyl, and butyl isocyanide bound to sperm whale myoglobin (Mb) reveal two major conformations. In the in conformer, His(E7) is in a "closed" position, forcing the ligand alkyl chain to point inward. In the out conformer, His(E7) is in an "open" position, allowing the ligand side chain to point outward. A progressive increase in the population of the out conformer is observed with increasing ligand length in P2(1) crystals of native Mb at pH 7.0. This switch from in to out with increasing ligand size also occurs in solution as measured by the decrease in the relative intensity of the low-frequency ( approximately 2075 cm(-1)) versus high-frequency ( approximately 2125 cm(-1)) isocyano bands. In contrast, all four isocyanides in P6 crystals of wild-type recombinant Mb occupy the in conformation. However, mutating either His64 to Ala, creating a "hole" to solvent, or Phe46 to Val, freeing rotation of His64, causes bound butyl isocyanide to point completely outward in P6 crystals. Thus, the unfavorable hindrance caused with crowding a large alkyl side chain into the distal pocket appears to be roughly equal to that for pushing open the His(E7) gate and is easily affected by crystal packing. This structural conclusion supports the "side path" kinetic mechanism for O(2) release, in which the dissociated ligand first moves toward the protein interior and then encounters steric resistance, which is roughly equal to that for escaping to solvent through the His(E7) channel.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1520-4995
pubmed:author
pubmed:issnType
Electronic
pubmed:day
22
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4977-86
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Straight-chain alkyl isocyanides open the distal histidine gate in crystal structures of myoglobin .
pubmed:affiliation
Department of Biochemistry and Cell Biology and W. M. Keck Center for Computational Biology, Rice University, Houston, Texas 77005, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural