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Molecular Model of Human CYP21 Based on Mammalian CYP2C5: Structural Features Correlate with Clinical Severity of Mutations Causing Congenital Adrenal Hyperplasia

Overview of attention for article published in Molecular Endocrinology, June 2006
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Title
Molecular Model of Human CYP21 Based on Mammalian CYP2C5: Structural Features Correlate with Clinical Severity of Mutations Causing Congenital Adrenal Hyperplasia
Published in
Molecular Endocrinology, June 2006
DOI 10.1210/me.2006-0172
Pubmed ID
Authors

Tiina Robins, Jonas Carlsson, Maria Sunnerhagen, Anna Wedell, Bengt Persson

Abstract

Enhanced understanding of structure-function relationships of human 21-hydroxylase, CYP21, is required to better understand the molecular causes of congenital adrenal hyperplasia. To this end, a structural model of human CYP21 was calculated based on the crystal structure of rabbit CYP2C5. All but two known allelic variants of missense type, a total of 60 disease-causing mutations and six normal variants, were analyzed using this model. A structural explanation for the corresponding phenotype was found for all but two mutants for which available clinical data are also discrepant with in vitro enzyme activity. Calculations of protein stability of modeled mutants were found to correlate inversely with the corresponding clinical severity. Putative structurally important residues were identified to be involved in heme and substrate binding, redox partner interaction, and enzyme catalysis using docking calculations and analysis of structurally determined homologous cytochrome P450s (CYPs). Functional and structural consequences of seven novel mutations, V139E, C147R, R233G, T295N, L308F, R366C, and M473I, detected in Scandinavian patients with suspected congenital adrenal hyperplasia of different severity, were predicted using molecular modeling. Structural features deduced from the models are in good correlation with clinical severity of CYP21 mutants, which shows the applicability of a modeling approach in assessment of new CYP21 mutations.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 25 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 4%
Germany 1 4%
Argentina 1 4%
Unknown 22 88%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 4 16%
Other 3 12%
Researcher 3 12%
Student > Doctoral Student 2 8%
Student > Bachelor 2 8%
Other 9 36%
Unknown 2 8%
Readers by discipline Count As %
Agricultural and Biological Sciences 8 32%
Biochemistry, Genetics and Molecular Biology 6 24%
Medicine and Dentistry 4 16%
Chemistry 2 8%
Pharmacology, Toxicology and Pharmaceutical Science 1 4%
Other 1 4%
Unknown 3 12%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 15 December 2006.
All research outputs
#17,289,387
of 25,377,790 outputs
Outputs from Molecular Endocrinology
#7,980
of 9,960 outputs
Outputs of similar age
#78,337
of 88,160 outputs
Outputs of similar age from Molecular Endocrinology
#64
of 75 outputs
Altmetric has tracked 25,377,790 research outputs across all sources so far. This one is in the 21st percentile – i.e., 21% of other outputs scored the same or lower than it.
So far Altmetric has tracked 9,960 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.6. This one is in the 13th percentile – i.e., 13% of its peers scored the same or lower than it.
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 88,160 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 5th percentile – i.e., 5% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 75 others from the same source and published within six weeks on either side of this one. This one is in the 5th percentile – i.e., 5% of its contemporaries scored the same or lower than it.