Disease relevance of HLCS

• OBJECTIVE: Multiple carboxylase deficiency (MCD, MIM:253270) is a common organic aciduria and caused by deficiency of either biotinidase or holocarboxylase synthetase (HLCS; EC 6.3.4.10) [1].
• Recently certain mutants of the Escherichia coli biotin protein ligase have been shown to mediate "promiscuous" biotinylation of proteins [2].
• Thus, in Alphaproteobacteria, BioR seems to have assumed the role of the biotin regulator that in most other bacteria is fulfilled by the dual function biotin-protein ligase BirA having the DNA-binding helix-turn-helix domain [3].

Psychiatry related information on HLCS

• Each patient completed standard self-administered psychologic tests to evaluate mood disturbance (Profile of Mood States [POMS]) and responsibility taken for overall health care (Health Locus of Control [HLCS]) [4].

High impact information on HLCS

• BPL catalyzes the covalent attachment of a single biotin to the fusion protein in vivo [5].
• A plasmid encoding both a biotin acceptor peptide-GLuc fusion protein as well as the enzyme biotin protein ligase (BPL) is engineered by using GLuc cDNA as a starting template [5].
• Enzymatic attachment of biotin to proteins requires the interaction of a distinct domain of the acceptor protein (the "biotin domain") with the enzyme, biotin protein ligase, that catalyzes this essential and rare post-translational modification [6].
• The unusual and insufficient response of this patient to biotin treatment can be explained by the effect of the combination of the common HLCS allele IVS10 +5 g>a on one chromosome and a truncating mutation on the other [7].
• The different phenotypes (early and late presenting) may be related to a spectrum of mutations in HLCS gene [1].

References