5YNI

Crystal structure of MERS-CoV nsp16/nsp10 complex bound to SAM and m7GpppG

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d5ynia_	Alpha and beta proteins (a/b)	S-adenosyl-L-methionine-dependent methyltransferases	S-adenosyl-L-methionine-dependent methyltransferases	mRNA cap methylase	automated matches	(Human betacoronavirus 2c EMC/2012 ) [TaxId: 1235996 ],	SCOPe (2.08)
B	d5ynib_	Small proteins	Coronavirus NSP10-like	Coronavirus NSP10-like	Coronavirus NSP10-like	Nonstructural protein 10, NSP10	(Human betacoronavirus 2c EMC/2012 ) [TaxId: 1235996 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	S-adenosyl-L-methionine-dependent methyltransferases	8090804	3000118	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	SARS coronavirus NSP10-like	8076501	3000547	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	NSP13	e5yniA1	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: S-adenosyl-L-methionine-dependent methyltransferases	F: NSP13	ECOD (1.6)
B	NSP10	e5yniB1	A: few secondary structure elements	X: Coronavirus NSP10-like (From Topology)	H: Coronavirus NSP10-like (From Topology)	T: Coronavirus NSP10-like	F: NSP10	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.40.50.150	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	Vaccinia Virus protein VP39	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF06460	Coronavirus 2'-O-methyltransferase (CoV_Methyltr_2)	Coronavirus 2'-O-methyltransferase	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 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

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	nsp16 protein	3'-5'-RNA exonuclease activity catalytic activity, acting on RNA RNA exonuclease activity, producing 5'-phosphomonoesters catalytic activity, acting on a nucleic acid 3'-5' exonuclease activity RNA exonuclease activity RNA nuclease activity hydrolase activity exonuclease activity, active with either ribo- or deoxyribonucleic acids and producing 5'-phosphomonoesters nuclease activity hydrolase activity, acting on ester bonds exonuclease activity catalytic activity binding 3'-5'-RNA exonuclease activity catalytic activity, acting on RNA RNA exonuclease activity, producing 5'-phosphomonoesters catalytic activity, acting on a nucleic acid 3'-5' exonuclease activity RNA exonuclease activity RNA nuclease activity hydrolase activity exonuclease activity, active with either ribo- or deoxyribonucleic acids and producing 5'-phosphomonoesters nuclease activity hydrolase activity, acting on ester bonds exonuclease activity catalytic activity binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding adenyl nucleotide binding ATP binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding ATP-dependent activity, acting on DNA DNA helicase activity catalytic activity, acting on DNA 5'-3' DNA helicase activity helicase activity ATP-dependent activity RNA methyltransferase activity transferase activity, transferring one-carbon groups transferase activity S-adenosylmethionine-dependent methyltransferase activity mRNA 5'-cap (guanine-N7-)-methyltransferase activity N-methyltransferase activity methyltransferase activity mRNA methyltransferase activity peptidase activity omega peptidase activity catalytic activity, acting on a protein RNA helicase activity ATP-dependent activity, acting on RNA endonuclease activity identical protein binding protein binding O-methyltransferase activity mRNA (nucleoside-2'-O-)-methyltransferase activity 5'-3' RNA polymerase activity RNA polymerase activity RNA-dependent RNA polymerase activity nucleotidyltransferase activity transferase activity, transferring phosphorus-containing groups cysteine-type peptidase activity cysteine-type endopeptidase activity endopeptidase activity lyase activity RNA binding nucleic acid binding single-stranded RNA binding ubiquitin-like protein peptidase activity cysteine-type deubiquitinase activity deubiquitinase activity G-quadruplex RNA binding cation binding transition metal ion binding zinc ion binding metal ion binding	RNA metabolic process viral life cycle primary metabolic process nucleobase-containing compound biosynthetic process macromolecule biosynthetic process nucleic acid metabolic process RNA biosynthetic process nucleobase-containing compound metabolic process nucleic acid biosynthetic process viral genome replication biosynthetic process viral RNA genome replication viral process metabolic process RNA metabolic process viral life cycle primary metabolic process nucleobase-containing compound biosynthetic process macromolecule biosynthetic process nucleic acid metabolic process RNA biosynthetic process nucleobase-containing compound metabolic process nucleic acid biosynthetic process viral genome replication biosynthetic process viral RNA genome replication viral process metabolic process cellular process macromolecule metabolic process symbiont-mediated suppression of host signal transduction pathway symbiont-mediated perturbation of host NF-kappaB cascade symbiont-mediated perturbation of host cellular process biological process involved in interspecies interaction between organisms symbiont-mediated perturbation of host process symbiont-mediated perturbation of host signal transduction pathway symbiont-mediated suppression of host NF-kappaB cascade modulation of process of another organism biological process involved in interaction with host biological process involved in symbiotic interaction symbiont-mediated perturbation of host defense response symbiont-mediated suppression of host ISG15-protein conjugation response to host defenses response to stimulus response to other organism symbiont-mediated perturbation of host immune response symbiont-mediated perturbation of host defenses response to defenses of other organism response to external stimulus response to biotic stimulus symbiont-mediated suppression of host immune response symbiont-mediated suppression of host innate immune response symbiont-mediated suppression of host defenses symbiont-mediated perturbation of host innate immune response response to host response to external biotic stimulus viral gene expression viral protein processing modulation by virus of host process virus-mediated perturbation of host defense response modulation by virus of host cellular process symbiont-mediated suppression of host interferon-mediated signaling pathway symbiont-mediated suppression of host type I interferon-mediated signaling pathway gene expression DNA-templated transcription symbiont-mediated degradation of host mRNA symbiont-mediated perturbation of host ubiquitin-like protein modification catabolic process regulation of cellular process autophagy positive regulation of biological process regulation of autophagy positive regulation of metabolic process induction by virus of host autophagy process utilizing autophagic mechanism positive regulation of cellular process positive regulation of autophagy regulation of biological process modulation by virus of host autophagy biological regulation regulation of catabolic process positive regulation of catabolic process regulation of metabolic process viral translational frameshifting viral translation 7-methylguanosine mRNA capping 7-methylguanosine RNA capping RNA capping mRNA processing mRNA metabolic process RNA 5'-end processing RNA processing proteolysis protein metabolic process	host intracellular membrane-bounded organelle host cellular component host intracellular part host cell endoplasmic reticulum-Golgi intermediate compartment cellular anatomical structure host cell cytoplasm host cell part host intracellular region host cell cytoplasm part host intracellular organelle host cell perinuclear region of cytoplasm membrane intracellular anatomical structure cytoplasm host intracellular membrane-bounded organelle host cellular component host intracellular part host cell endoplasmic reticulum-Golgi intermediate compartment cellular anatomical structure host cell cytoplasm host cell part host intracellular region host cell cytoplasm part host intracellular organelle host cell perinuclear region of cytoplasm membrane intracellular anatomical structure cytoplasm membrane-bounded organelle intracellular organelle protein-containing complex organelle nucleus nuclear protein-containing complex intracellular membrane-bounded organelle mRNA capping enzyme complex host cell membrane
B	nsp10 protein	peptidase activity omega peptidase activity catalytic activity, acting on a protein hydrolase activity catalytic activity transferase activity, transferring one-carbon groups transferase activity methyltransferase activity cysteine-type peptidase activity cysteine-type endopeptidase activity endopeptidase activity RNA binding binding organic cyclic compound binding peptidase activity omega peptidase activity catalytic activity, acting on a protein hydrolase activity catalytic activity transferase activity, transferring one-carbon groups transferase activity methyltransferase activity cysteine-type peptidase activity cysteine-type endopeptidase activity endopeptidase activity RNA binding binding organic cyclic compound binding nucleic acid binding single-stranded RNA binding ubiquitin-like protein peptidase activity cysteine-type deubiquitinase activity deubiquitinase activity G-quadruplex RNA binding cation binding transition metal ion binding zinc ion binding ion binding metal ion binding small molecule binding	methylation metabolic process cellular process symbiont-mediated perturbation of host defense response symbiont-mediated suppression of host ISG15-protein conjugation response to host defenses biological process involved in interspecies interaction between organisms response to stimulus response to other organism symbiont-mediated perturbation of host immune response symbiont-mediated perturbation of host defenses response to defenses of other organism response to external stimulus biological process involved in interaction with host methylation metabolic process cellular process symbiont-mediated perturbation of host defense response symbiont-mediated suppression of host ISG15-protein conjugation response to host defenses biological process involved in interspecies interaction between organisms response to stimulus response to other organism symbiont-mediated perturbation of host immune response symbiont-mediated perturbation of host defenses response to defenses of other organism response to external stimulus biological process involved in interaction with host response to biotic stimulus biological process involved in symbiotic interaction symbiont-mediated suppression of host immune response symbiont-mediated suppression of host innate immune response symbiont-mediated perturbation of host process symbiont-mediated suppression of host defenses symbiont-mediated perturbation of host innate immune response response to host response to external biotic stimulus modulation of process of another organism viral gene expression viral protein processing viral process symbiont-mediated perturbation of host cellular process symbiont-mediated degradation of host mRNA modulation by virus of host process virus-mediated perturbation of host defense response modulation by virus of host cellular process symbiont-mediated perturbation of host ubiquitin-like protein modification catabolic process regulation of cellular process autophagy positive regulation of biological process regulation of autophagy positive regulation of metabolic process induction by virus of host autophagy process utilizing autophagic mechanism positive regulation of cellular process positive regulation of autophagy regulation of biological process modulation by virus of host autophagy biological regulation regulation of catabolic process positive regulation of catabolic process regulation of metabolic process symbiont-mediated suppression of host signal transduction pathway symbiont-mediated suppression of host interferon-mediated signaling pathway symbiont-mediated suppression of host type I interferon-mediated signaling pathway symbiont-mediated perturbation of host signal transduction pathway viral genome replication viral life cycle viral translational frameshifting viral translation proteolysis primary metabolic process protein metabolic process macromolecule metabolic process	cellular anatomical structure membrane host cellular component host intracellular part host cell perinuclear region of cytoplasm host cell cytoplasm host cell part host intracellular region host cell cytoplasm part host cell membrane

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR022733	DPUP/SUD, C-terminal, betacoronavirus	Domain
A	IPR042515	Non-structural protein NSP15, N-terminal domain superfamily, coronavirus	Homologous Superfamily
A	IPR043174	Non-structural protein NSP15, middle domain superfamily	Homologous Superfamily
A	IPR044315	Nonstructural protein 14, betacoronavirus	Domain
A	IPR038123	Non-structural protein NSP4, C-terminal superfamily, coronavirus	Homologous Superfamily
A	IPR042570	Non-structural protein NSP3, nucleic acid-binding domain superfamily, betacoronavirus	Homologous Superfamily
A	IPR043178	Papain-like protease, thumb domain superfamily, coronavirus	Homologous Superfamily
A	IPR046441	RNA-dependent RNA polymerase, coronavirus	Domain
A	IPR044388	Non-structural protein 2, MERS-CoV-like	Domain
A	IPR044863	Nidovirus RdRp-associated nucleotidyl transferase (NiRAN) domain	Domain
A	IPR044343	Nonstructural protein 13, 1B domain, coronavirus	Domain
A	IPR037227	Endoribonuclease EndoU-like	Homologous Superfamily
A	IPR027352	Nonstructural protein 13, zinc-binding domain, coronavirus-like	Domain
A	IPR009003	Peptidase S1, PA clan	Homologous Superfamily
A	IPR013016	Peptidase C16, coronavirus	Domain
A	IPR009466	Non-structural protein 14, coronavirus	Domain
A	IPR044357	NSP3, first ubiquitin-like (Ubl) domain, coronavirus	Domain
A	IPR046436	Nidovirus 3'-5' exoribonuclease domain	Domain
A	IPR047570	NSP12, interface domain, coronavirus	Domain
A	IPR018995	RNA synthesis protein NSP10, coronavirus	Domain
A	IPR043615	Nonstructural protein 2, N-terminal domain, coronavirus	Domain
A	IPR050534	Coronaviruses polyprotein 1ab	Family
A	IPR043177	Papain-like protease, N-terminal domain superfamily, coronavirus	Homologous Superfamily
A	IPR043606	Coronavirus replicase NSP15, N-terminal oligomerization	Domain
A	IPR044330	Nonstructural protein 15, N-terminal domain, alpha/beta-coronavirus	Domain
A	IPR044350	RNA-dependent RNA polymerase, Middle East respiratory syndrome-related coronavirus	Domain
A	IPR041679	DNA2/NAM7 helicase-like, C-terminal	Domain
A	IPR024375	Non-structural protein NSP3, SUD-M domain, betacoronavirus	Domain
A	IPR014828	Non-structural protein NSP7, coronavirus	Domain
A	IPR043503	Papain-like viral protease, palm and finger domains, coronavirus	Homologous Superfamily
A	IPR014829	Non-structural protein NSP8, coronavirus	Domain
A	IPR036499	Non-structural protein NSP9 superfamily, coronavirus	Homologous Superfamily
A	IPR029063	S-adenosyl-L-methionine-dependent methyltransferase superfamily	Homologous Superfamily
A	IPR043502	DNA/RNA polymerase superfamily	Homologous Superfamily
A	IPR008740	Peptidase C30, coronavirus	Domain
A	IPR036333	RNA synthesis protein NSP10 superfamily, coronavirus	Homologous Superfamily
A	IPR047573	Non-structural protein 2, middle domain, coronavirus	Domain
A	IPR049894	Coronavirus NSP3, 3Ecto domain	Domain
A	IPR043472	Macro domain-like	Homologous Superfamily
A	IPR043609	NendoU domain, nidovirus	Domain
A	IPR032592	Non-structural protein NSP3, nucleic acid-binding domain, betacoronavirus	Domain
A	IPR043613	Non-structural protein 2, C-terminal domain, coronavirus	Domain
A	IPR038083	Non-structural protein NSP3A domain-like superfamily	Homologous Superfamily
A	IPR043504	Peptidase S1, PA clan, chymotrypsin-like fold	Homologous Superfamily
A	IPR048673	Nonstructural protein 13, stalk domain, coronavirus	Domain
A	IPR046435	NSP14, guanine-N7-methyltransferase domain, coronavirus	Domain
A	IPR009469	RNA-dependent RNA polymerase, N-terminal, coronavirus	Domain
A	IPR043611	Coronavirus replicase NSP3, C-terminal	Domain
A	IPR047566	Coronavirus replicase NSP3, Y domain	Domain
A	IPR048672	Nonstructural protein 13, zinc-binding domain, coronavirus	Domain
A	IPR043612	Non-structural protein NSP4, N-terminal, coronavirus	Domain
A	IPR027417	P-loop containing nucleoside triphosphate hydrolase	Homologous Superfamily
A	IPR043608	Nonstructural protein 15, middle domain, coronavirus	Domain
A	IPR044353	NSP3, second ubiquitin-like (Ubl) domain, coronavirus	Domain
A	IPR044382	NSP3, SUD-C domain, MERS-CoV-like	Domain
A	IPR037204	Non-structural protein NSP7 superfamily, coronavirus	Homologous Superfamily
A	IPR046443	NSP1, globular domain, alpha/betacoronavirus	Domain
A	IPR043610	Non-structural protein 6, coronavirus	Domain
A	IPR027351	(+) RNA virus helicase core domain	Domain
A	IPR044322	Nonstructural protein 15, middle domain, alpha/betacoronavirus	Domain
A	IPR009461	Non-structural protein NSP16, coronavirus-like	Domain
A	IPR043477	Peptidase C30, domain 3, coronavirus	Homologous Superfamily
A	IPR038400	Non-structural protein NSP3, SUD-M domain superfamily, betacoronavirus	Homologous Superfamily
A	IPR046442	NSP1, C-terminal domain, betacoronavirus	Domain
A	IPR001205	RNA-directed RNA polymerase, C-terminal domain	Domain
A	IPR014822	Non-structural protein NSP9, coronavirus	Domain
A	IPR021590	NSP1, globular domain, betacoronavirus	Domain
A	IPR044367	Non-structural protein 6, betacoronavirus	Domain
A	IPR037230	Non-structural protein NSP8 superfamily, coronavirus	Homologous Superfamily
A	IPR046440	Arterivirus Nsp11 N-terminal/Coronavirus NSP15 middle domain	Domain
A	IPR032505	Non-structural protein NSP4, C-terminal, coronavirus	Domain
A	IPR046438	Nidovirus 2-O-methyltransferase	Domain
A	IPR002589	Macro domain	Domain
A	IPR047567	Non-structural protein NSP3, group 2-specific marker domain, betacoronavirus	Domain
A	IPR044371	Non-structural protein 3, X-domain-like	Domain
A	IPR007094	RNA-directed RNA polymerase, catalytic domain	Domain
B	IPR022733	DPUP/SUD, C-terminal, betacoronavirus	Domain
B	IPR043611	Coronavirus replicase NSP3, C-terminal	Domain
B	IPR038123	Non-structural protein NSP4, C-terminal superfamily, coronavirus	Homologous Superfamily
B	IPR042570	Non-structural protein NSP3, nucleic acid-binding domain superfamily, betacoronavirus	Homologous Superfamily
B	IPR047566	Coronavirus replicase NSP3, Y domain	Domain
B	IPR043178	Papain-like protease, thumb domain superfamily, coronavirus	Homologous Superfamily
B	IPR044388	Non-structural protein 2, MERS-CoV-like	Domain
B	IPR043612	Non-structural protein NSP4, N-terminal, coronavirus	Domain
B	IPR044353	NSP3, second ubiquitin-like (Ubl) domain, coronavirus	Domain
B	IPR009003	Peptidase S1, PA clan	Homologous Superfamily
B	IPR044382	NSP3, SUD-C domain, MERS-CoV-like	Domain
B	IPR013016	Peptidase C16, coronavirus	Domain
B	IPR037204	Non-structural protein NSP7 superfamily, coronavirus	Homologous Superfamily
B	IPR044357	NSP3, first ubiquitin-like (Ubl) domain, coronavirus	Domain
B	IPR046443	NSP1, globular domain, alpha/betacoronavirus	Domain
B	IPR043610	Non-structural protein 6, coronavirus	Domain
B	IPR043477	Peptidase C30, domain 3, coronavirus	Homologous Superfamily
B	IPR018995	RNA synthesis protein NSP10, coronavirus	Domain
B	IPR038400	Non-structural protein NSP3, SUD-M domain superfamily, betacoronavirus	Homologous Superfamily
B	IPR046442	NSP1, C-terminal domain, betacoronavirus	Domain
B	IPR043615	Nonstructural protein 2, N-terminal domain, coronavirus	Domain
B	IPR043177	Papain-like protease, N-terminal domain superfamily, coronavirus	Homologous Superfamily
B	IPR014822	Non-structural protein NSP9, coronavirus	Domain
B	IPR021590	NSP1, globular domain, betacoronavirus	Domain
B	IPR024375	Non-structural protein NSP3, SUD-M domain, betacoronavirus	Domain
B	IPR044367	Non-structural protein 6, betacoronavirus	Domain
B	IPR037230	Non-structural protein NSP8 superfamily, coronavirus	Homologous Superfamily
B	IPR014828	Non-structural protein NSP7, coronavirus	Domain
B	IPR032505	Non-structural protein NSP4, C-terminal, coronavirus	Domain
B	IPR043503	Papain-like viral protease, palm and finger domains, coronavirus	Homologous Superfamily
B	IPR014829	Non-structural protein NSP8, coronavirus	Domain
B	IPR036499	Non-structural protein NSP9 superfamily, coronavirus	Homologous Superfamily
B	IPR002589	Macro domain	Domain
B	IPR047567	Non-structural protein NSP3, group 2-specific marker domain, betacoronavirus	Domain
B	IPR008740	Peptidase C30, coronavirus	Domain
B	IPR036333	RNA synthesis protein NSP10 superfamily, coronavirus	Homologous Superfamily
B	IPR047573	Non-structural protein 2, middle domain, coronavirus	Domain
B	IPR049894	Coronavirus NSP3, 3Ecto domain	Domain
B	IPR043472	Macro domain-like	Homologous Superfamily
B	IPR044371	Non-structural protein 3, X-domain-like	Domain
B	IPR032592	Non-structural protein NSP3, nucleic acid-binding domain, betacoronavirus	Domain
B	IPR043613	Non-structural protein 2, C-terminal domain, coronavirus	Domain
B	IPR038083	Non-structural protein NSP3A domain-like superfamily	Homologous Superfamily
B	IPR043504	Peptidase S1, PA clan, chymotrypsin-like fold	Homologous Superfamily