Microbial biotin protein ligases aid in understanding holocarboxylase synthetase deficiency.

Abstract

The attachment of biotin onto the biotin-dependent enzymes is catalysed by biotin protein ligase (BPL), also known as holocarboxylase synthase HCS in mammals. Mammals contain five biotin-enzymes that participate in a number of important metabolic pathways such as fatty acid biogenesis, gluconeogenesis and amino acid catabolism. All mammalian biotin-enzymes are post-translationally biotinylated, and therefore activated, through the action of a single HCS. Substrate recognition by BPLs occurs through conserved structural cues that govern the specificity of biotinylation. Defects in biotin metabolism, including HCS, give rise to multiple carboxylase deficiency (MCD). Here we review the literature on this important enzyme. In particular, we focus on the new information that has been learned about BPL's from a number of recently published protein structures. Through molecular modelling studies insights into the structural basis of HCS deficiency in MCD are discussed.

• Authors: Nicole R Pendini, Lisa M Bailey, Grant W Booker, Matthew C Wilce, John C Wallace, Steven W Polyak
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) 2008 Jul-Aug Vol. 1784 Issue 7-8 Pg. 973-82 ISSN: 0006-3002 [Print] Netherlands
• PMID: 18442489 (Publication Type: Journal Article, Review)

Chemical References

• Escherichia coli Proteins
• Repressor Proteins
• Carbon-Nitrogen Ligases
• birA protein, E coli

Topics

• Animals
• Carbon-Nitrogen Ligases (chemistry, metabolism)
• Escherichia coli Proteins (chemistry, metabolism)
• Holocarboxylase Synthetase Deficiency (enzymology)
• Humans
• Models, Molecular
• Protein Conformation
• Repressor Proteins (chemistry, metabolism)
• Substrate Specificity