Comment to Santos et al., "hyper-IgD and periodic fever syndrome: a new MVK mutation (p.R277G) associated with a severe phenotype".

Abstract

We performed molecular modeling analysis onto a novel mutation in the gene MVK, described by Santos et al., found to be causative of a severe form of Hyper-IgD/Mevalonate Kinase Deficiency. The mutation p.R277G, in our analysis, lowers the binding affinity for some enzyme's substrates. Interestingly, we found that p.R277G mutation inhibits binding of Isopentenyl Pyrophosphate (IPP) (binding free energy=0 kcal/mol), one of isoprenoids responsible for feedback-inhibition of MVK. IPP is known to be an activator of a specific class of T-cells and we can hypothesize that increased levels of this metabolite generate an aberrant immune system response. Indeed other experiments are needed to verify this hypothesis; however, this work demonstrates usefulness of molecular modeling in generating novel pathogenic hypothesis.

• Authors: Ruda de Luna Almeida Santos, Sergio Crovella, Fulvio Celsi
• Journal: Gene (Gene) Vol. 559 Issue 1 Pg. 99-101 (Mar 15 2015) ISSN: 1879-0038 [Electronic] Netherlands
• PMID: 25620160 (Publication Type: Letter, Comment)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Immunoglobulin D
• Phosphotransferases (Alcohol Group Acceptor)

Topics

• Fever (genetics)
• Humans
• Immunoglobulin D (genetics)
• Male
• Mutation, Missense
• Phosphotransferases (Alcohol Group Acceptor) (genetics)