Molecule Information

General Information of the Molecule (ID: Mol00804)

Name	Arylamine N-acetyltransferase 1 (NAT1) ,Mycolicibacterium smegmatis
Synonyms	NAT Click to Show/Hide
Molecule Type	Protein
Gene Name	nat
Sequence	MAMDLGGYLTRIGLDGRPRPDLGTLHAIVAAHNRSIPFENLDPLLGIPVADLSAEALFAK LVDRRRGGYCYEHNGLLGYVLEELGFEVERLSGRVVWMRADDAPLPAQTHNVLSVAVPGA DGRYLVDVGFGGQTLTSPIRLEAGPVQQTRHEPYRLTRHGDDHTLAAQVRGEWQPLYTFT TEPRPRIDLEVGSWYVSTHPGSHFVTGLTVAVVTDDARYNLRGRNLAVHRSGATEHIRFD SAAQVLDAIVNRFGIDLGDLAGRDVQARVAEVLDT Click to Show/Hide
Function	Catalyzes the transfer of the acetyl group from acetyl coenzyme A to the free amino group of arylamines and hydrazines. Substrates include isoniazid, anisidine, and 4-aminoveratrole, and to a much lesser extent, p-aminobenzoic acid. Click to Show/Hide
Uniprot ID	NAT_MYCSM
*Click to Show/Hide the Complete Species Lineage*
Kingdom: N.A. Phylum: Actinobacteria Class: Actinomycetia Order: Corynebacteriales Family: Mycobacteriaceae Genus: Mycolicibacterium Species: Mycolicibacterium smegmatis

Type(s) of Resistant Mechanism of This Molecule

DISM: Drug Inactivation by Structure Modification

Drug Resistance Data Categorized by Drug

Approved Drug(s)

1 drug(s) in total

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Isoniazid

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Drug Inactivation by Structure Modification (DISM)		Click to Show/Hide
Disease Class: HIV-infected patients with tuberculosis			[1]
Resistant Disease	HIV-infected patients with tuberculosis [ICD-11: 1C60.0]		Disease Info
Resistant Drug	Isoniazid		Drug Info
Molecule Alteration	Expression	Up-regulation
Experimental Note	Discovered Using In-vivo Testing Model
Cell Pathway Regulation	Cell growth	Activation	hsa05200
In Vitro Model	Mycobacterium tuberculosis H37Rv		83332
Experiment for Molecule Alteration	SDS-PAGE assay
Experiment for Drug Resistance	Titertek multiskan assay
Mechanism Description	Arylamine N-acetyltransferase (NAT), a drug-metabolizing enzyme of MTB, can acetylate INH, transferring an acetyl group from acetyl coenzyme A to the terminal nitrogen of the drug, which in its N-acetylated form is therapeutically inactive. The overexpression of NAT in Mycobacterium smegmatis showed increased resistance to INH; in addition, when the gene was knocked-out, the bacteria exhibited increased sensitivity to INH.

References

Ref 1	Cloning and characterization of arylamine N-acetyltransferase genes from Mycobacterium smegmatis and Mycobacterium tuberculosis: increased expression results in isoniazid resistance. J Bacteriol. 1999 Feb;181(4):1343-7. doi: 10.1128/JB.181.4.1343-1347.1999.