6WKS

Structure of SARS-CoV-2 nsp16/nsp10 in complex with RNA cap analogue (m7GpppA) and S-adenosylmethionine


Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

ChainsTypeFamily Name Domain Identifier Family IdentifierProvenance Source (Version)
A [auth AAA]SCOP2B SuperfamilyS-adenosyl-L-methionine-dependent methyltransferases 8092457 3000118 SCOP2B (2022-06-29)
B [auth BBB]SCOP2B SuperfamilySARS coronavirus NSP10-like 8092459 3000547 SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

ChainsFamily NameDomain Identifier ArchitecturePossible HomologyHomologyTopologyFamilyProvenance Source (Version)
A [auth AAA]NSP13e6wksAAA1 A: a/b three-layered sandwichesX: Rossmann-likeH: Rossmann-relatedT: S-adenosyl-L-methionine-dependent methyltransferasesF: NSP13ECOD (1.6)
B [auth BBB]NSP10e6wksBBB1 A: few secondary structure elementsX: Coronavirus NSP10-like (From Topology)H: Coronavirus NSP10-like (From Topology)T: Coronavirus NSP10-likeF: NSP10ECOD (1.6)

Protein Family Annotation Pfam Database Homepage

ChainsAccessionNameDescriptionCommentsSource
A [auth AAA]PF06460Coronavirus 2'-O-methyltransferase (CoV_Methyltr_2)Coronavirus 2'-O-methyltransferaseThis domain covers the NSP16 region of the coronavirus polyprotein. The SARS-CoV RNA cap SAM-dependent (nucleoside-2'-O-)-methyltransferase (2'-O-MTase) is a heterodimer comprising SARS-CoV nsp10 and nsp16. When bound to nsp10, nsp16 is active as a t ...This domain covers the NSP16 region of the coronavirus polyprotein. The SARS-CoV RNA cap SAM-dependent (nucleoside-2'-O-)-methyltransferase (2'-O-MTase) is a heterodimer comprising SARS-CoV nsp10 and nsp16. When bound to nsp10, nsp16 is active as a type-0 RNA cap-dependent 2'-O-MTase, ie., active only when the cap guanine is methylated at its N7 position. Nsp10 binds to nsp16 through an activation surface area in nsp10, and the resulting complex exhibits RNA cap (nucleoside-2'-O)-methyltransferase activity. Nsp10 is a double zinc finger protein together with nsp4, nsp5, nsp12, nsp14, and nsp16, nsp10 has been found to be essential in the assembly of a functional replication/transcription complex. NSP16 plays a key role in viral replication as it is involved in immune response evasion through the 2'-O-methylation of coronavirus RNA, which is essential for preventing recognition by the host. It mimics the human protein CMTr1 and, unlike CMTr1, it requires NSP10 as a binding partner to activate its enzymatic activity [4]. Nsp16 adopts a typical fold of the S-adenosylmethionine-dependent methyltransferase (SAM) family as defined initially for the catechol O-MTase but it lacks several elements of the canonical MTase fold, such as helices B and C. The nsp16 topology matches those of dengue virus NS5 N-terminal domain and of vaccinia virus VP39 MTases [1,2, 3]. Structural analysis in NSP16 from SARS-CoV-2 identified a cryptic pocket (also present in other coronavirus such as SARS-CoV-1 and MERS) not present in human CMTr1, and the fact that NSP16 is one of the most conserved proteins of SARS-CoV-2 and related viruses, make it an interesting target for developing new antiviral treatment for COVID-19 and other diseases caused by coronaviruses [5].
Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

ChainsPolymerMolecular FunctionBiological ProcessCellular Component
A [auth AAA]2'-O-methyltransferase
B [auth BBB]Non-structural protein 10

InterPro: Protein Family Classification InterPro Database Homepage

ChainsAccessionNameType
A [auth AAA]IPR022733DPUP/SUD, C-terminal, betacoronavirusDomain
A [auth AAA]IPR042515Non-structural protein NSP15, N-terminal domain superfamily, coronavirusHomologous Superfamily
A [auth AAA]IPR043174Non-structural protein NSP15, middle domain superfamilyHomologous Superfamily
A [auth AAA]IPR044315Nonstructural protein 14, betacoronavirusDomain
A [auth AAA]IPR038123Non-structural protein NSP4, C-terminal superfamily, coronavirusHomologous Superfamily
A [auth AAA]IPR042570Non-structural protein NSP3, nucleic acid-binding domain superfamily, betacoronavirusHomologous Superfamily
A [auth AAA]IPR043178Papain-like protease, thumb domain superfamily, coronavirusHomologous Superfamily
A [auth AAA]IPR046441RNA-dependent RNA polymerase, coronavirusDomain
A [auth AAA]IPR044863Nidovirus RdRp-associated nucleotidyl transferase (NiRAN) domainDomain
A [auth AAA]IPR044343Nonstructural protein 13, 1B domain, coronavirusDomain
A [auth AAA]IPR038166Polyprotein cleavage domain PL2pro superfamily, betacoronavirusHomologous Superfamily
A [auth AAA]IPR037227Endoribonuclease EndoU-likeHomologous Superfamily
A [auth AAA]IPR027352Nonstructural protein 13, zinc-binding domain, coronavirus-likeDomain
A [auth AAA]IPR009003Peptidase S1, PA clanHomologous Superfamily
A [auth AAA]IPR013016Peptidase C16, coronavirusDomain
A [auth AAA]IPR009466Non-structural protein 14, coronavirusDomain
A [auth AAA]IPR044357NSP3, first ubiquitin-like (Ubl) domain, coronavirusDomain
A [auth AAA]IPR046436Nidovirus 3'-5' exoribonuclease domainDomain
A [auth AAA]IPR047570NSP12, interface domain, coronavirusDomain
A [auth AAA]IPR018995RNA synthesis protein NSP10, coronavirusDomain
A [auth AAA]IPR043615Nonstructural protein 2, N-terminal domain, coronavirusDomain
A [auth AAA]IPR050534Coronaviruses polyprotein 1abFamily
A [auth AAA]IPR043177Papain-like protease, N-terminal domain superfamily, coronavirusHomologous Superfamily
A [auth AAA]IPR043606Coronavirus replicase NSP15, N-terminal oligomerizationDomain
A [auth AAA]IPR044330Nonstructural protein 15, N-terminal domain, alpha/beta-coronavirusDomain
A [auth AAA]IPR041679DNA2/NAM7 helicase-like, C-terminalDomain
A [auth AAA]IPR024375Non-structural protein NSP3, SUD-M domain, betacoronavirusDomain
A [auth AAA]IPR014828Non-structural protein NSP7, coronavirusDomain
A [auth AAA]IPR043503Papain-like viral protease, palm and finger domains, coronavirusHomologous Superfamily
A [auth AAA]IPR014829Non-structural protein NSP8, coronavirusDomain
A [auth AAA]IPR036499Non-structural protein NSP9 superfamily, coronavirusHomologous Superfamily
A [auth AAA]IPR029063S-adenosyl-L-methionine-dependent methyltransferase superfamilyHomologous Superfamily
A [auth AAA]IPR044389Non-structural protein 2, SARS-CoV-likeDomain
A [auth AAA]IPR043502DNA/RNA polymerase superfamilyHomologous Superfamily
A [auth AAA]IPR008740Peptidase C30, coronavirusDomain
A [auth AAA]IPR036333RNA synthesis protein NSP10 superfamily, coronavirusHomologous Superfamily
A [auth AAA]IPR047573Non-structural protein 2, middle domain, coronavirusDomain
A [auth AAA]IPR049894Coronavirus NSP3, 3Ecto domainDomain
A [auth AAA]IPR043472Macro domain-likeHomologous Superfamily
A [auth AAA]IPR043609NendoU domain, nidovirusDomain
A [auth AAA]IPR032592Non-structural protein NSP3, nucleic acid-binding domain, betacoronavirusDomain
A [auth AAA]IPR043613Non-structural protein 2, C-terminal domain, coronavirusDomain
A [auth AAA]IPR038083Non-structural protein NSP3A domain-like superfamilyHomologous Superfamily
A [auth AAA]IPR043504Peptidase S1, PA clan, chymotrypsin-like foldHomologous Superfamily
A [auth AAA]IPR044351RNA-dependent RNA polymerase, SARS-CoV-likeDomain
A [auth AAA]IPR024358Non-structural protein NSP3, N-terminal, betacoronavirusDomain
A [auth AAA]IPR048673Nonstructural protein 13, stalk domain, coronavirusDomain
A [auth AAA]IPR046435NSP14, guanine-N7-methyltransferase domain, coronavirusDomain
A [auth AAA]IPR009469RNA-dependent RNA polymerase, N-terminal, coronavirusDomain
A [auth AAA]IPR043611Coronavirus replicase NSP3, C-terminalDomain
A [auth AAA]IPR044864Non-structural protein NSP3, SUD-N (Mac2) domain, betacoronavirusDomain
A [auth AAA]IPR047566Coronavirus replicase NSP3, Y domainDomain
A [auth AAA]IPR048672Nonstructural protein 13, zinc-binding domain, coronavirusDomain
A [auth AAA]IPR043612Non-structural protein NSP4, N-terminal, coronavirusDomain
A [auth AAA]IPR027417P-loop containing nucleoside triphosphate hydrolaseHomologous Superfamily
A [auth AAA]IPR043608Nonstructural protein 15, middle domain, coronavirusDomain
A [auth AAA]IPR044353NSP3, second ubiquitin-like (Ubl) domain, coronavirusDomain
A [auth AAA]IPR037204Non-structural protein NSP7 superfamily, coronavirusHomologous Superfamily
A [auth AAA]IPR046443NSP1, globular domain, alpha/betacoronavirusDomain
A [auth AAA]IPR043610Non-structural protein 6, coronavirusDomain
A [auth AAA]IPR027351(+) RNA virus helicase core domainDomain
A [auth AAA]IPR044322Nonstructural protein 15, middle domain, alpha/betacoronavirusDomain
A [auth AAA]IPR009461Non-structural protein NSP16, coronavirus-likeDomain
A [auth AAA]IPR043477Peptidase C30, domain 3, coronavirusHomologous Superfamily
A [auth AAA]IPR043478Non-structural protein NSP3, SUD-N (Mac2) domain superfamily, betacoronavirusHomologous Superfamily
A [auth AAA]IPR038400Non-structural protein NSP3, SUD-M domain superfamily, betacoronavirusHomologous Superfamily
A [auth AAA]IPR046442NSP1, C-terminal domain, betacoronavirusDomain
A [auth AAA]IPR001205RNA-directed RNA polymerase, C-terminal domainDomain
A [auth AAA]IPR044401NSP15, NendoU domain, coronavirusDomain
A [auth AAA]IPR014822Non-structural protein NSP9, coronavirusDomain
A [auth AAA]IPR038030NSP1 globular domain superfamily, betacoronavirusHomologous Superfamily
A [auth AAA]IPR021590NSP1, globular domain, betacoronavirusDomain
A [auth AAA]IPR044367Non-structural protein 6, betacoronavirusDomain
A [auth AAA]IPR037230Non-structural protein NSP8 superfamily, coronavirusHomologous Superfamily
A [auth AAA]IPR046440Arterivirus Nsp11 N-terminal/Coronavirus NSP15 middle domainDomain
A [auth AAA]IPR032505Non-structural protein NSP4, C-terminal, coronavirusDomain
A [auth AAA]IPR046438Nidovirus 2-O-methyltransferaseDomain
A [auth AAA]IPR002589Macro domainDomain
A [auth AAA]IPR047567Non-structural protein NSP3, group 2-specific marker domain, betacoronavirusDomain
A [auth AAA]IPR044371Non-structural protein 3, X-domain-likeDomain
A [auth AAA]IPR007094RNA-directed RNA polymerase, catalytic domainDomain
B [auth BBB]IPR022733DPUP/SUD, C-terminal, betacoronavirusDomain
B [auth BBB]IPR042515Non-structural protein NSP15, N-terminal domain superfamily, coronavirusHomologous Superfamily
B [auth BBB]IPR043174Non-structural protein NSP15, middle domain superfamilyHomologous Superfamily
B [auth BBB]IPR044315Nonstructural protein 14, betacoronavirusDomain
B [auth BBB]IPR038123Non-structural protein NSP4, C-terminal superfamily, coronavirusHomologous Superfamily
B [auth BBB]IPR042570Non-structural protein NSP3, nucleic acid-binding domain superfamily, betacoronavirusHomologous Superfamily
B [auth BBB]IPR043178Papain-like protease, thumb domain superfamily, coronavirusHomologous Superfamily
B [auth BBB]IPR046441RNA-dependent RNA polymerase, coronavirusDomain
B [auth BBB]IPR044863Nidovirus RdRp-associated nucleotidyl transferase (NiRAN) domainDomain
B [auth BBB]IPR044343Nonstructural protein 13, 1B domain, coronavirusDomain
B [auth BBB]IPR038166Polyprotein cleavage domain PL2pro superfamily, betacoronavirusHomologous Superfamily
B [auth BBB]IPR037227Endoribonuclease EndoU-likeHomologous Superfamily
B [auth BBB]IPR027352Nonstructural protein 13, zinc-binding domain, coronavirus-likeDomain
B [auth BBB]IPR009003Peptidase S1, PA clanHomologous Superfamily
B [auth BBB]IPR013016Peptidase C16, coronavirusDomain
B [auth BBB]IPR009466Non-structural protein 14, coronavirusDomain
B [auth BBB]IPR044357NSP3, first ubiquitin-like (Ubl) domain, coronavirusDomain
B [auth BBB]IPR046436Nidovirus 3'-5' exoribonuclease domainDomain
B [auth BBB]IPR047570NSP12, interface domain, coronavirusDomain
B [auth BBB]IPR018995RNA synthesis protein NSP10, coronavirusDomain
B [auth BBB]IPR043615Nonstructural protein 2, N-terminal domain, coronavirusDomain
B [auth BBB]IPR050534Coronaviruses polyprotein 1abFamily
B [auth BBB]IPR043177Papain-like protease, N-terminal domain superfamily, coronavirusHomologous Superfamily
B [auth BBB]IPR043606Coronavirus replicase NSP15, N-terminal oligomerizationDomain
B [auth BBB]IPR044330Nonstructural protein 15, N-terminal domain, alpha/beta-coronavirusDomain
B [auth BBB]IPR041679DNA2/NAM7 helicase-like, C-terminalDomain
B [auth BBB]IPR024375Non-structural protein NSP3, SUD-M domain, betacoronavirusDomain
B [auth BBB]IPR014828Non-structural protein NSP7, coronavirusDomain
B [auth BBB]IPR043503Papain-like viral protease, palm and finger domains, coronavirusHomologous Superfamily
B [auth BBB]IPR014829Non-structural protein NSP8, coronavirusDomain
B [auth BBB]IPR036499Non-structural protein NSP9 superfamily, coronavirusHomologous Superfamily
B [auth BBB]IPR029063S-adenosyl-L-methionine-dependent methyltransferase superfamilyHomologous Superfamily
B [auth BBB]IPR044389Non-structural protein 2, SARS-CoV-likeDomain
B [auth BBB]IPR043502DNA/RNA polymerase superfamilyHomologous Superfamily
B [auth BBB]IPR008740Peptidase C30, coronavirusDomain
B [auth BBB]IPR036333RNA synthesis protein NSP10 superfamily, coronavirusHomologous Superfamily
B [auth BBB]IPR047573Non-structural protein 2, middle domain, coronavirusDomain
B [auth BBB]IPR049894Coronavirus NSP3, 3Ecto domainDomain
B [auth BBB]IPR043472Macro domain-likeHomologous Superfamily
B [auth BBB]IPR043609NendoU domain, nidovirusDomain
B [auth BBB]IPR032592Non-structural protein NSP3, nucleic acid-binding domain, betacoronavirusDomain
B [auth BBB]IPR043613Non-structural protein 2, C-terminal domain, coronavirusDomain
B [auth BBB]IPR038083Non-structural protein NSP3A domain-like superfamilyHomologous Superfamily
B [auth BBB]IPR043504Peptidase S1, PA clan, chymotrypsin-like foldHomologous Superfamily
B [auth BBB]IPR044351RNA-dependent RNA polymerase, SARS-CoV-likeDomain
B [auth BBB]IPR024358Non-structural protein NSP3, N-terminal, betacoronavirusDomain
B [auth BBB]IPR048673Nonstructural protein 13, stalk domain, coronavirusDomain
B [auth BBB]IPR046435NSP14, guanine-N7-methyltransferase domain, coronavirusDomain
B [auth BBB]IPR009469RNA-dependent RNA polymerase, N-terminal, coronavirusDomain
B [auth BBB]IPR043611Coronavirus replicase NSP3, C-terminalDomain
B [auth BBB]IPR044864Non-structural protein NSP3, SUD-N (Mac2) domain, betacoronavirusDomain
B [auth BBB]IPR047566Coronavirus replicase NSP3, Y domainDomain
B [auth BBB]IPR048672Nonstructural protein 13, zinc-binding domain, coronavirusDomain
B [auth BBB]IPR043612Non-structural protein NSP4, N-terminal, coronavirusDomain
B [auth BBB]IPR027417P-loop containing nucleoside triphosphate hydrolaseHomologous Superfamily
B [auth BBB]IPR043608Nonstructural protein 15, middle domain, coronavirusDomain
B [auth BBB]IPR044353NSP3, second ubiquitin-like (Ubl) domain, coronavirusDomain
B [auth BBB]IPR037204Non-structural protein NSP7 superfamily, coronavirusHomologous Superfamily
B [auth BBB]IPR046443NSP1, globular domain, alpha/betacoronavirusDomain
B [auth BBB]IPR043610Non-structural protein 6, coronavirusDomain
B [auth BBB]IPR027351(+) RNA virus helicase core domainDomain
B [auth BBB]IPR044322Nonstructural protein 15, middle domain, alpha/betacoronavirusDomain
B [auth BBB]IPR009461Non-structural protein NSP16, coronavirus-likeDomain
B [auth BBB]IPR043477Peptidase C30, domain 3, coronavirusHomologous Superfamily
B [auth BBB]IPR043478Non-structural protein NSP3, SUD-N (Mac2) domain superfamily, betacoronavirusHomologous Superfamily
B [auth BBB]IPR038400Non-structural protein NSP3, SUD-M domain superfamily, betacoronavirusHomologous Superfamily
B [auth BBB]IPR046442NSP1, C-terminal domain, betacoronavirusDomain
B [auth BBB]IPR001205RNA-directed RNA polymerase, C-terminal domainDomain
B [auth BBB]IPR044401NSP15, NendoU domain, coronavirusDomain
B [auth BBB]IPR014822Non-structural protein NSP9, coronavirusDomain
B [auth BBB]IPR038030NSP1 globular domain superfamily, betacoronavirusHomologous Superfamily
B [auth BBB]IPR021590NSP1, globular domain, betacoronavirusDomain
B [auth BBB]IPR044367Non-structural protein 6, betacoronavirusDomain
B [auth BBB]IPR037230Non-structural protein NSP8 superfamily, coronavirusHomologous Superfamily
B [auth BBB]IPR046440Arterivirus Nsp11 N-terminal/Coronavirus NSP15 middle domainDomain
B [auth BBB]IPR032505Non-structural protein NSP4, C-terminal, coronavirusDomain
B [auth BBB]IPR046438Nidovirus 2-O-methyltransferaseDomain
B [auth BBB]IPR002589Macro domainDomain
B [auth BBB]IPR047567Non-structural protein NSP3, group 2-specific marker domain, betacoronavirusDomain
B [auth BBB]IPR044371Non-structural protein 3, X-domain-likeDomain
B [auth BBB]IPR007094RNA-directed RNA polymerase, catalytic domainDomain
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