Enzymatic activities and characteristics of coronavirus nsp protein domains

ActivityLocation and designationProtein familyArchitectureCommentsReferences
Papain-like proteinaseOne or two PLpro domains within nsp3Deubiquitinating enzyme familyFinger-palm-thumbFingertips contain zinc-binding domain 5, 33, 56
ADP-ribose 1"-phosphataseADRP (or X) domain within nsp3Macro-HS2A-fold familyThree-layered α/β/αAlso found in other plus-strand RNA viruses 53, 58
3C-like cysteine proteinasensp5 (3CLpro or main protease, Mpro)Two-β-barrel proteinase familyTwelve antiparallel β-strandsExtra, α-helical, carboxyl-terminal domain III 3, 4, 95
RNA-dependent RNA polymeraseRdRp domain within nsp12Viral RdRp familyFinger-palm-thumb (predicted)RdRp motif VI signature GDD replaced with SDD 19, 87
5′-to-3′ helicase (associated, NTPase, and RNA 5′-triphosphatase activities)HEL domain within nsp13Superfamily 1 helicaseModeled to Escherichia coli Rep helicaseAdjacent to amino-proximal, binuclear, zinc-binding domain 9, 35, 36, 70
3′-to-5′ exonucleaseExoN domain within nsp14DEDD superfamilyHexahelical bundle (predicted)Unable to cleave ribose 2′-O-methylated RNA substrates 45, 75
Uridylate-specific endoribonucleaseNendoU domain within nsp15XendoU familyWing-body-wing (butterfly fold)Active in hexameric form; RNA bound to internal cavity 10, 11, 31, 34, 56a, 88
S-adenosylmethionine-dependent 2′-O-methyltransferasensp16 (MT)Rrmj methyltransferase familyMethyltransferase fold (predicted)Activity yet to be determined 75, 86