Abstract
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In the MEROPS database peptidases and peptidase homologues are grouped into clans and families. Clans are groups of families for which there is evidence of common ancestry based on a common structural fold:
- Each clan is identified with two letters, the first representing the catalytic type of the families included in the clan (with the letter 'P' being used for a clan containing families of more than one of the catalytic types serine, threonine and cysteine). Some families cannot yet be assigned to clans, and when a formal assignment is required, such a family is described as belonging to clan A-, C-, M-, S-, T- or U-, according to the catalytic type. Some clans are divided into subclans because there is evidence of a very ancient divergence within the clan, for example MA(E), the gluzincins, and MA(M), the metzincins.
- Peptidase families are grouped by their catalytic type, the first character representing the catalytic type: A, aspartic; C, cysteine; G, glutamic acid; M, metallo; S, serine; T, threonine; and U, unknown. The serine, threonine and cysteine peptidases utilise the amino acid as a nucleophile and form an acyl intermediate - these peptidases can also readily act as transferases. In the case of aspartic, glutamic and metallopeptidases, the nucleophile is an activated water molecule.
In many instances the structural protein fold that characterises the clan or family may have lost its catalytic activity, yet retain its function in protein recognition and binding.
Metalloproteases are the most diverse of the four main types of protease, with more than 50 families identified to date. In these enzymes, a divalent cation, usually zinc, activates the water molecule. The metal ion is held in place by amino acid ligands, usually three in number. The known metal ligands are His, Glu, Asp or Lys and at least one other residue is required for catalysis, which may play an electrophillic role.
Of the known metalloproteases, around half contain an HEXXH motif, which has been shown in crystallographic studies to form part of the metal-binding site [1]. The HEXXH motif is relatively common, but can be more stringently defined for metalloproteases as 'abXHEbbHbc', where 'a' is most often valine or threonine and forms part of the S1' subsite in thermolysin and neprilysin, 'b' is an uncharged residue, and 'c' a hydrophobic residue. Proline is never found in this site, possibly because it would break the helical structure adopted by this motif in metalloproteases [1].
This entry represents a clade of the amidohydrolases. They classified as metallopeptidases belonging to MEROPS peptidase family M20 (clan MH), subfamily M20D. Included within this group are hydrolases of hippurate (N-benzylglycine), indoleacetic acid (IAA) N-conjugates of amino acids, N-acetyl-L-amino acids and aminobenzoylglutamate. These hydrolases are of the carboxypeptidase-type, most likely utilizing a zinc ion in the active site.
In higher plants, the growth hormone indole-3-acetic acid (IAA or auxin) is stored conjugated to sugar moieties via an ester linkage or to amino acids or peptides via an amide. More than 95% of the hormone in a plant can be found in the conjugated form, leaving only a small amount of free hormone available to stimulate and control cellular growth. The overall levels of active IAA in a plant can be controlled not only by the amount of IAA synthesized, but also by the quantity of IAA that is released from the conjugated state into the free state. Amidohydrolases cleave the amide bond between the auxin and the conjugated amino acid. Several IAA amidohydrolases have been isolated from Arabidopsis thaliana (Mouse-ear cress), each of these enzymes has different substrate specificities. The A. thaliana IAA amidohydrolase, IAR3, is able to cleave IAA-Alanine, while products of the other amidohydrolase genes, known as the ILR1-like family of hydrolases (ILR1, ILL1, ILL2, ILL3, and ILL5), cleave primarily IAA-Phenylalanine and IAA-Leucine [2].
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