ArticleBiochemistry2008
The histamine N-methyltransferase T105I polymorphism affects active site structure and dynamics.
Article in Biochemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Human variability in isoform-specific UDP-glucuronosyltransferases: markers of acute and chronic exposure, polymorphisms and uncertainty factors.Archives of toxicology · 2020Pooled it
- Impact of AOC1 and HNMT Variants on the Therapeutic Outcomes of a Histamine Reducing Diet in Autism Spectrum Disorder.Journal of molecular neuroscience : MN · 2025Article
- HistamineInternational journal of molecular sciences · 2019Review
- Article
- The diamine oxidase gene is associated with hypersensitivity response to non-steroidal anti-inflammatory drugs.PloS one · 2012Article
- Ligands in PSI structures.Acta crystallographica. Section F, Structural biology and crystallization communications · 2010Article
- Polymorphisms and disease: hotspots of inactivation in methyltransferases.Trends in biochemical sciences · 2010Article
- Dynameomics: a comprehensive database of protein dynamics.Structure (London, England : 1993) · 2010Article
- Histamine N-methyltransferase Thr105Ile is not associated with Parkinson's disease or essential tremor.Parkinsonism & related disorders · 2010Article
- The R46Q, R131Q and R154H polymorphs of human DNA glycosylase/beta-lyase hOgg1 severely distort the active site and DNA recognition site but do not cause unfolding.Journal of the American Chemical Society · 2009Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.