Bacterial mycothiol S-conjugate amidase family

Chemistry: molecular biology and microbiology – Enzyme – proenzyme; compositions thereof; process for... – Hydrolase

Reexamination Certificate

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C435S230000

Reexamination Certificate

active

10427218

ABSTRACT:
The present invention provides a family of bacterial acyl glucosaminylinositol amidases with amidase activity against S-conjugate amides, particularly mycothiol-derived S-conjugate amides. The invention amidases are characterized by a highly conserved 20 amino acid N-terminal region and four highly conserved histidine-containing regions and by having amidase activity, particularly amide hydrolase activity. The invention further provides methods for using the invention amidases in drug screening assays to determine compounds with antibiotic activity or compounds that inhibit activity or production of endogenous acyl glucosaminyl inositol amidase in bacteria. The invention further provides methods for detoxifying a toxic substance by contacting the toxic substance with an invention amidase, for example, by expression of the amidase under environmental conditions in a bacterium.

REFERENCES:
Cole et al.,Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence,Nature 393:537-544 (1998).
Newton et al.,Mycothiol biochemistry,Arch. Microbiol. 178:388-394 (2002.
Cole et al., Data Base PIR-68, Accession No. H70894 (Jul. 17, 1998).
Cole et al., “Deciphering the Body ofMycobacterium tuberculosisfrom the Complete Genome Sequence,” Nature, Jul. 19, 1998, vol. 393, No. 6685, pp. 537-544.
Newton at al., “A Novel Mycothiol-Dependent Detoxification Pathway in Mycobacteria Involving Mycothiol S-Conjugate Amidase,”Biochemistry,2000, vol. 39, pp. 10739-10746.
Robinson, K., “Direct Submission”, GenBank Database, Accession No. MLU15183, Mar. 9, 1995.

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