What is a decarboxylase? Formally defined, a decarboxylase is a carbon-carbon lyase that add or remove a carboxyl group from an organic compound. A well known example is pyruvate decarboxylase, an enzyme that is involved in the fermentation process in yeast. Pyruvate decarboxylase converts pyruvate into carbon dioxide and acetaldehyde using a non-oxidative mechanism, with TPP as a cofactor and requiring MG2+ (Nelson & Cox, 2005).

What is ACMSD? α-Amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) is a widespread enzyme found in many bacterial species and all eukaryotic organisms whose genomes have been sequenced. The crystal structure is a dimer, each with a metal (Zn) bound in the active site (Figure 1). Each monomer contains a distorted TIM barrel structure and an insertion region. The isoforms are known ACMSD I and ACMSD II. Transcripts of ACMSD II are alternatively spliced, thus the protein differs from ACMSD I in the N-terminal region. The enzyme, ACMSD I is found mainly in the kidney as well as in lower amounts in the liver and brain, whereas ACMSD II is present only the in kidney and liver and at equivalent levels (Pucci et al, 2007).

 

 

Figure 1. Crystal Structure of ACMSD Is a dimer. The active site, contains a Zn (orange spheres) in each monomer. The monomers have a TIM barrel fold. Monomer A (blue) and monomer B (hot pink).

 

 

Importance of ACMSD. ACMSD is relevant to health as a drug therapy target, as well as being an enzyme with an activity that is important to reducing environmental pollution by nitroaromatic compounds.

Amidohydrolase superfamily. ACMSD therefore is the first characterized member of the amidohydrolase superfamily that represents a C-C breaking activity. Sequence analysis suggests that ACMSD is related to a large metal-dependent hydrolase superfamily that includes urease, adenosine deaminase, phosphotriesterase, and dihydroorotase, among others. Many members of this enzyme family are well characterized functionally and structurally. Enzymes in this superfamily adopt the (β/α)8-barrel fold with eight strands of parallel β-sheet flanked on the outside with α-helices (known also as TIM-barrel fold). The active site of these enzymes in this superfamily contain either a binuclear or mononuclear metal center which is catalytically essential. Protein residues that function as metal ligands typically include an HxH metal-binding motif at the end of the first ‚ strand, one histidine at the end of the fifth β-strand, one histidine at β-strand 6, and an aspartic acid from the end of the eighth β-strand (Li, et al, 2006). All of these important amino acid residues can be seen in the structure analysis of ACMSD.