|Family type peptidase
|M81.001 - microcystinase MlrC (Sphingomonas sp. ACM-3962), MEROPS Accession MER0167712 (peptidase unit: 1-325)
|Content of family
|Peptidase family M81 contains metallopeptidases.
Identifier created: MEROPS 9.4 (31 January 2011)
Microcystins are peptide toxins produced by cyanobacteria which can cause hepatotoxicity by inhibiting protein phosphatases. Microcystins are heptapeptides containing unusual amino acids. Microcystin LR (cyclo(NH2-Adda-isoGlu-methyldehydroAla-Leu-beta-methylAsp-Arg)) is one of the commonest microcystins, persisting in contaminated water supplies for weeks. Efforts to find a method to remove the microcystin led to the discovery of a species of Sphingomonas which can utilize the microcystin as a source of carbon and nitrogen. The bacterium has three specialized peptidase to degrade it. Microcystinase (G05.004) converts the cyclic peptide to a linear peptide, MlrB peptidase (S12.009) cleaves the methyldehydroAla-Leu bond to generate two fragments (Bourne et al., 1996), and the tetrapeptide is further degraded by the MlrC peptidase (M81.001; Bourne et al., 2001) but the exact cleavage position is unknown.
|From the deduced crystal structure of a homologue from Mesorhizobium sp. BNC1, a single zinc ion is bound by Asp38, His140 and His162. The histidines are well conserved, but the aspartic acid is not.
|Activities and specificities
|The MlrC peptidase from Sphingopyxis degrades both microcystins LR and LA (Ho et al., 2007).
|The MlrC peptidase is assumed to be a metallopeptidase because of inhibition by metal chelators (Bourne et al., 2001).
|The tertiary structure has been solved for a biochemically uncharacterized homologue from Mesorhizobium sp. BNC1. The structure has been deposited in the Protein Data Bank but has not yet been published. The structure show a two-domain protein, with each domain containing a beta sheet surrounded by helices. The active site containing the zinc ion is between the domains. The fold is unlike that of any other peptidase, but related to ABC ribose transporters, alanine racemase, maltose operon transcriptional repressors, and chemotaxis protein Chey. Consequently, the structure of the Mesorhizobium homologue is the type structure for clan MT.