The variable response to warfarin treatment often has a genetic basis. A protein homology model of human vitamin K epoxide reductase, subunit 1 (VKORC1), was generated to elucidate the mechanism of warfarin resistance observed in a patient with the Val66Met mutation. The VKORC1 homology model comprises four transmembrane (TM) helical domains and a half helical lid domain. Cys132 and Cys135, located in the N-terminal end of TM-4, are linked through a disulfide bond. Two distinct binding sites for warfarin were identified. Site-1, which binds vitamin K epoxide (KO) in a catalytically favorable orientation, shows higher affinity for S-warfarin compared with R-warfarin. Site-2, positioned in the domain occupied by the hydrophobic tail of KO, binds both warfarin enantiomers with similar affinity. Displacement of Arg37 occurs in the Val66Met mutant, blocking access of warfarin (but not KO) to Site-1, consistent with clinical observation of warfarin resistance.
Pharmacology, Toxicology and Pharmaceutical Science
6
18%
Medicine and Dentistry
4
12%
Biochemistry, Genetics and Molecular Biology
3
9%
Chemistry
3
9%
Agricultural and Biological Sciences
2
6%
Other
4
12%
Unknown
11
33%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 6. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 04 May 2020.
All research outputs
#8,554,251
of 32,375,021 outputs
Outputs from Pharmacogenetics and Genomics
#182
of 969 outputs
Outputs of similar age
#102,875
of 433,203 outputs
Outputs of similar age from Pharmacogenetics and Genomics
#3
of 21 outputs
Altmetric has tracked 32,375,021 research outputs across all sources so far. This one has received more attention than most of these and is in the 73rd percentile.
So far Altmetric has tracked 969 research outputs from this source. They receive a mean Attention Score of 4.0. This one has done well, scoring higher than 81% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 433,203 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 76% of its contemporaries.
We're also able to compare this research output to 21 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 85% of its contemporaries.
