6c2g | pdb_00006c2g
Human triosephosphate isomerase mutant V231M
Structural highlights
Disease[TPIS_HUMAN] Defects in TPI1 are the cause of triosephosphate isomerase deficiency (TPI deficiency) [MIM:190450]. TPI deficiency is an autosomal recessive disorder. It is the most severe clinical disorder of glycolysis. It is associated with neonatal jaundice, chronic hemolytic anemia, progressive neuromuscular dysfunction, cardiomyopathy and increased susceptibility to infection. Publication Abstract from PubMedHuman triosephosphate isomerase (TIM) deficiency is a very rare disease, but there are several mutations reported to be causing the illness. In this work, we produced nine recombinant human triosephosphate isomerases which have the mutations reported to produce TIM deficiency. These enzymes were characterized biophysically and biochemically to determine their kinetic and stability parameters, and also to substitute TIM activity in supporting the growth of an Escherichia coli strain lacking the tim gene. Our results allowed us to rate the deleteriousness of the human TIM mutants based on the type and severity of the alterations observed, to classify four "unknown severity mutants" with altered residues in positions 62, 72, 122 and 154 and to explain in structural terms the mutation V231M, the most affected mutant from the kinetic point of view and the only homozygous mutation reported besides E104D. Differential effects on enzyme stability and kinetic parameters of mutants related to human triosephosphate isomerase deficiency.,Cabrera N, Torres-Larios A, Garcia-Torres I, Enriquez-Flores S, Perez-Montfort R Biochim Biophys Acta. 2018 Mar 20;1862(6):1401-1409. doi:, 10.1016/j.bbagen.2018.03.019. PMID:29571745[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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