Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-1-15
pubmed:abstractText
Histamine N-methyltransferase (HNMT) is the primary enzyme responsible for inactivating histamine in the mammalian brain. The human HNMT gene contains a common threonine-isoleucine polymorphism at residue 105, distal from the active site. The 105I variant has decreased activity and lower protein levels than the 105T protein. Crystal structures of both variants have been determined but reveal little regarding how the T105I polymorphism affects activity. We performed molecular dynamics simulations for both 105T and 105I at 37 degrees C to explore the structural and dynamic consequences of the polymorphism. The simulations indicate that replacing Thr with the larger Ile residue leads to greater burial of residue 105 and heightened intramolecular interactions between residue 105 and residues within helix alpha3 and strand beta3. This altered, tighter packing is translated to the active site, resulting in the reorientation of several cosubstrate-binding residues. The simulations also show that the hydrophobic histamine-binding domain in both proteins undergoes a large-scale breathing motion that exposes key catalytic residues and lowers the hydrophobicity of the substrate-binding site.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/18154359-10654665, http://linkedlifedata.com/resource/pubmed/commentcorrection/18154359-10752634, http://linkedlifedata.com/resource/pubmed/commentcorrection/18154359-10803682, http://linkedlifedata.com/resource/pubmed/commentcorrection/18154359-11172935, http://linkedlifedata.com/resource/pubmed/commentcorrection/18154359-11566133, http://linkedlifedata.com/resource/pubmed/commentcorrection/18154359-11640972, http://linkedlifedata.com/resource/pubmed/commentcorrection/18154359-11640975, http://linkedlifedata.com/resource/pubmed/commentcorrection/18154359-11880199, http://linkedlifedata.com/resource/pubmed/commentcorrection/18154359-12360102, http://linkedlifedata.com/resource/pubmed/commentcorrection/18154359-12417108, http://linkedlifedata.com/resource/pubmed/commentcorrection/18154359-12835614, http://linkedlifedata.com/resource/pubmed/commentcorrection/18154359-12867290, http://linkedlifedata.com/resource/pubmed/commentcorrection/18154359-12882233, http://linkedlifedata.com/resource/pubmed/commentcorrection/18154359-14966473, http://linkedlifedata.com/resource/pubmed/commentcorrection/18154359-15264254, http://linkedlifedata.com/resource/pubmed/commentcorrection/18154359-15283920, http://linkedlifedata.com/resource/pubmed/commentcorrection/18154359-15457404, http://linkedlifedata.com/resource/pubmed/commentcorrection/18154359-15551002, http://linkedlifedata.com/resource/pubmed/commentcorrection/18154359-15693910, http://linkedlifedata.com/resource/pubmed/commentcorrection/18154359-15770103, http://linkedlifedata.com/resource/pubmed/commentcorrection/18154359-16168438, http://linkedlifedata.com/resource/pubmed/commentcorrection/18154359-16205835, http://linkedlifedata.com/resource/pubmed/commentcorrection/18154359-16259739, http://linkedlifedata.com/resource/pubmed/commentcorrection/18154359-16475806, http://linkedlifedata.com/resource/pubmed/commentcorrection/18154359-16890992, http://linkedlifedata.com/resource/pubmed/commentcorrection/18154359-17023991, http://linkedlifedata.com/resource/pubmed/commentcorrection/18154359-17275092, http://linkedlifedata.com/resource/pubmed/commentcorrection/18154359-17390750, http://linkedlifedata.com/resource/pubmed/commentcorrection/18154359-3345617, http://linkedlifedata.com/resource/pubmed/commentcorrection/18154359-7563068, http://linkedlifedata.com/resource/pubmed/commentcorrection/18154359-7703232, http://linkedlifedata.com/resource/pubmed/commentcorrection/18154359-8145732, http://linkedlifedata.com/resource/pubmed/commentcorrection/18154359-8339926, http://linkedlifedata.com/resource/pubmed/commentcorrection/18154359-9148245, http://linkedlifedata.com/resource/pubmed/commentcorrection/18154359-9547362
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
47
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
893-901
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
The histamine N-methyltransferase T105I polymorphism affects active site structure and dynamics.
pubmed:affiliation
Department of Biochemistry, University of Washington, Box 355061, Seattle, Washington 98195-5061, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural