3M5M

Avoiding drug resistance against HCV NS3/4A protease inhibitors

External Resource: Annotation

Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Protein Modification Annotation

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	Peptidase_S29	e3m5mA1	A: beta barrels	X: cradle loop barrel	H: RIFT-related	T: FMN-binding split barrel	F: Peptidase_S29	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	2.40.10.120	Mainly Beta	Beta Barrel	Thrombin, subunit H		CATH (4.3.0)
A	2.40.10.10	Mainly Beta	Beta Barrel	Thrombin, subunit H	Trypsin-like serine proteases	CATH (4.3.0)
B	2.40.10.120	Mainly Beta	Beta Barrel	Thrombin, subunit H		CATH (4.3.0)
B	2.40.10.10	Mainly Beta	Beta Barrel	Thrombin, subunit H	Trypsin-like serine proteases	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B	PF02907	Hepatitis C virus NS3 protease (Peptidase_S29)	Hepatitis C virus NS3 protease	Hepatitis C virus NS3 protein is a serine protease which has a trypsin-like fold. The non-structural (NS) protein NS3 is one of the NS proteins involved in replication of the HCV genome. NS2-3 proteinase, a zinc-dependent enzyme, performs a single p ...	Hepatitis C virus NS3 protein is a serine protease which has a trypsin-like fold. The non-structural (NS) protein NS3 is one of the NS proteins involved in replication of the HCV genome. NS2-3 proteinase, a zinc-dependent enzyme, performs a single proteolytic cut to release the N-terminus of NS3. The action of NS3 proteinase (NS3P), which resides in the N-terminal one-third of the NS3 protein, then yields all remaining non-structural proteins. The C-terminal two-thirds of the NS3 protein contain a helicase. The functional relationship between the proteinase and helicase domains is unknown. NS3 has a structural zinc-binding site and requires cofactor NS4A.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B	NS3/4A	peptidase activity catalytic activity, acting on a protein serine hydrolase activity serine-type peptidase activity hydrolase activity serine-type endopeptidase activity catalytic activity endopeptidase activity binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding peptidase activity catalytic activity, acting on a protein serine hydrolase activity serine-type peptidase activity hydrolase activity serine-type endopeptidase activity catalytic activity endopeptidase 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 pyrophosphatase activity ribonucleoside triphosphate phosphatase activity hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides hydrolase activity, acting on acid anhydrides catalytic activity, acting on RNA catalytic activity, acting on a nucleic acid helicase activity RNA helicase activity ATP-dependent activity, acting on RNA ATP-dependent activity 5'-3' RNA polymerase activity RNA polymerase activity transferase activity RNA-dependent RNA polymerase activity nucleotidyltransferase activity transferase activity, transferring phosphorus-containing groups cysteine-type peptidase activity cysteine-type endopeptidase activity RNA binding nucleic acid binding passive transmembrane transporter activity channel activity transporter activity transmembrane transporter activity structural molecule activity cation binding transition metal ion binding zinc ion binding metal ion binding	cellular biosynthetic process cellular 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 cellular biosynthetic process cellular 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 perturbation of host cellular process biological process involved in interspecies interaction between organisms symbiont-mediated suppression of host JAK-STAT cascade biological process involved in interaction with host biological process involved in symbiotic interaction symbiont-mediated suppression of host signal transduction pathway symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT activity symbiont-mediated perturbation of host process symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity symbiont-mediated perturbation of host signal transduction pathway modulation of process of another organism symbiont-mediated suppression of host TRAF-mediated signal transduction apoptotic process cell death programmed cell death symbiont-mediated perturbation of host defense response response to host defenses response to stimulus response to other organism response to defenses of other organism modulation by virus of host process response to external stimulus virus-mediated perturbation of host defense response response to biotic stimulus response to host response to external biotic stimulus modulation by virus of host cellular process catabolic process regulation of cellular process autophagy positive regulation of biological process positive regulation of cellular metabolic process regulation of autophagy cellular catabolic process 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 cellular metabolic process regulation of catabolic process positive regulation of catabolic process regulation of cellular catabolic process positive regulation of cellular catabolic process regulation of metabolic process symbiont-mediated suppression of host type I interferon-mediated signaling pathway symbiont-mediated suppression of host interferon-mediated signaling pathway fusion of virus membrane with host endosome membrane membrane fusion involved in viral entry into host cell import into cell receptor-mediated endocytosis of virus by host cell transport establishment of localization vesicle-mediated transport localization symbiont entry into host cell clathrin-dependent endocytosis symbiont entry into host clathrin-dependent endocytosis of virus by host cell receptor-mediated endocytosis endocytosis endocytosis involved in viral entry into host cell transport of virus transmembrane transport monoatomic ion transmembrane transport monoatomic ion transport symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity symbiont-mediated suppression of host pathogen-associated molecular pattern receptor signaling pathway symbiont-mediated suppression of host immune response symbiont-mediated suppression of host innate immune response response to host immune response symbiont-mediated suppression of host defenses symbiont-mediated perturbation of host innate immune response symbiont-mediated perturbation of host immune response symbiont-mediated perturbation of host defenses symbiont-mediated suppression of cytoplasmic pattern recognition receptor signaling pathway virion attachment to host cell adhesion of symbiont to host cell adhesion of symbiont to host transformation of host cell by virus proteolysis protein metabolic process symbiont-mediated perturbation of host cell cycle progression symbiont-mediated perturbation of host cell cycle G1/S transition checkpoint	host cellular component host intracellular part host cell cytoplasm host cell part host cell lipid droplet host intracellular region cellular anatomical entity host cell cytoplasm part host intracellular membrane-bounded organelle host cell membrane host cell mitochondrion host intracellular organelle host cell mitochondrial envelope host cell mitochondrial membrane host cellular component host intracellular part host cell cytoplasm host cell part host cell lipid droplet host intracellular region cellular anatomical entity host cell cytoplasm part host intracellular membrane-bounded organelle host cell membrane host cell mitochondrion host intracellular organelle host cell mitochondrial envelope host cell mitochondrial membrane intracellular anatomical structure cytoplasm host cell endoplasmic reticulum host cell endomembrane system host cell endoplasmic reticulum membrane viral nucleocapsid viral capsid virion component cell periphery plasma membrane membrane host cell plasma membrane host cell perinuclear region of cytoplasm virion membrane lipid droplet intracellular organelle organelle intracellular non-membrane-bounded organelle non-membrane-bounded organelle host cell nucleus viral membrane viral envelope protein-containing complex ribonucleoprotein complex
C	FDEMEEC Peptide	peptidase activity catalytic activity, acting on a protein serine hydrolase activity serine-type peptidase activity hydrolase activity serine-type endopeptidase activity catalytic activity endopeptidase activity binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding peptidase activity catalytic activity, acting on a protein serine hydrolase activity serine-type peptidase activity hydrolase activity serine-type endopeptidase activity catalytic activity endopeptidase 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 pyrophosphatase activity ribonucleoside triphosphate phosphatase activity hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides hydrolase activity, acting on acid anhydrides catalytic activity, acting on RNA catalytic activity, acting on a nucleic acid helicase activity RNA helicase activity ATP-dependent activity, acting on RNA ATP-dependent activity 5'-3' RNA polymerase activity RNA polymerase activity transferase activity RNA-dependent RNA polymerase activity nucleotidyltransferase activity transferase activity, transferring phosphorus-containing groups cysteine-type peptidase activity cysteine-type endopeptidase activity RNA binding nucleic acid binding passive transmembrane transporter activity channel activity transporter activity transmembrane transporter activity structural molecule activity cation binding transition metal ion binding zinc ion binding metal ion binding	cellular biosynthetic process cellular 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 cellular biosynthetic process cellular 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 perturbation of host cellular process biological process involved in interspecies interaction between organisms symbiont-mediated suppression of host JAK-STAT cascade biological process involved in interaction with host biological process involved in symbiotic interaction symbiont-mediated suppression of host signal transduction pathway symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT activity symbiont-mediated perturbation of host process symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity symbiont-mediated perturbation of host signal transduction pathway modulation of process of another organism symbiont-mediated suppression of host TRAF-mediated signal transduction apoptotic process cell death programmed cell death symbiont-mediated perturbation of host defense response response to host defenses response to stimulus response to other organism response to defenses of other organism modulation by virus of host process response to external stimulus virus-mediated perturbation of host defense response response to biotic stimulus response to host response to external biotic stimulus modulation by virus of host cellular process catabolic process regulation of cellular process autophagy positive regulation of biological process positive regulation of cellular metabolic process regulation of autophagy cellular catabolic process 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 cellular metabolic process regulation of catabolic process positive regulation of catabolic process regulation of cellular catabolic process positive regulation of cellular catabolic process regulation of metabolic process symbiont-mediated suppression of host type I interferon-mediated signaling pathway symbiont-mediated suppression of host interferon-mediated signaling pathway fusion of virus membrane with host endosome membrane membrane fusion involved in viral entry into host cell import into cell receptor-mediated endocytosis of virus by host cell transport establishment of localization vesicle-mediated transport localization symbiont entry into host cell clathrin-dependent endocytosis symbiont entry into host clathrin-dependent endocytosis of virus by host cell receptor-mediated endocytosis endocytosis endocytosis involved in viral entry into host cell transport of virus transmembrane transport monoatomic ion transmembrane transport monoatomic ion transport symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity symbiont-mediated suppression of host pathogen-associated molecular pattern receptor signaling pathway symbiont-mediated suppression of host immune response symbiont-mediated suppression of host innate immune response response to host immune response symbiont-mediated suppression of host defenses symbiont-mediated perturbation of host innate immune response symbiont-mediated perturbation of host immune response symbiont-mediated perturbation of host defenses symbiont-mediated suppression of cytoplasmic pattern recognition receptor signaling pathway virion attachment to host cell adhesion of symbiont to host cell adhesion of symbiont to host transformation of host cell by virus proteolysis protein metabolic process symbiont-mediated perturbation of host cell cycle progression symbiont-mediated perturbation of host cell cycle G1/S transition checkpoint	host cellular component host intracellular part host cell cytoplasm host cell part host cell lipid droplet host intracellular region cellular anatomical entity host cell cytoplasm part host intracellular membrane-bounded organelle host cell membrane host cell mitochondrion host intracellular organelle host cell mitochondrial envelope host cell mitochondrial membrane host cellular component host intracellular part host cell cytoplasm host cell part host cell lipid droplet host intracellular region cellular anatomical entity host cell cytoplasm part host intracellular membrane-bounded organelle host cell membrane host cell mitochondrion host intracellular organelle host cell mitochondrial envelope host cell mitochondrial membrane intracellular anatomical structure cytoplasm host cell endoplasmic reticulum host cell endomembrane system host cell endoplasmic reticulum membrane viral nucleocapsid viral capsid virion component cell periphery plasma membrane membrane host cell plasma membrane host cell perinuclear region of cytoplasm virion membrane lipid droplet intracellular organelle organelle intracellular non-membrane-bounded organelle non-membrane-bounded organelle host cell nucleus viral membrane viral envelope protein-containing complex ribonucleoprotein complex

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B	IPR002522	Hepatitis C virus, Core protein, N-terminal	Domain
A, B	IPR043128	Reverse transcriptase/Diguanylate cyclase domain	Homologous Superfamily
A, B	IPR054175	NS3 RNA helicase, C-terminal helical domain	Domain
A, B	IPR038568	Hepatitis C virus NS5A, 1B domain superfamily	Homologous Superfamily
A, B	IPR027417	P-loop containing nucleoside triphosphate hydrolase	Homologous Superfamily
A, B	IPR009003	Peptidase S1, PA clan	Homologous Superfamily
A, B	IPR001650	Helicase, C-terminal domain-like	Domain
A, B	IPR014001	Helicase superfamily 1/2, ATP-binding domain	Domain
A, B	IPR002868	Hepatitis C virus, Non-structural 5a protein	Domain
A, B	IPR038170	NS5A domain 1a superfamily	Homologous Superfamily
A, B	IPR002518	Hepatitis C virus, Non-structural protein NS2	Domain
A, B	IPR013192	Hepatitis C virus, Non-structural 5a protein, domain 1a	Domain
A, B	IPR002521	Hepatitis C virus, Core protein, C-terminal	Domain
A, B	IPR042209	Hepatitis C virus non-structural protein NS2, N-terminal domain	Homologous Superfamily
A, B	IPR000745	Hepatitis C virus, Non-structural protein NS4a	Domain
A, B	IPR011492	Non-structural protein NS3-like, DEAD box helicase, flavivirus	Domain
A, B	IPR042205	Hepatitis C virus non-structural protein NS2, C-terminal domain	Homologous Superfamily
A, B	IPR002166	RNA dependent RNA polymerase, hepatitis C virus	Family
A, B	IPR002519	Hepatitis C virus, Envelope glycoprotein E1	Domain
A, B	IPR043502	DNA/RNA polymerase superfamily	Homologous Superfamily
A, B	IPR044896	Hepatitis C virus core protein, chain A superfamily	Homologous Superfamily
A, B	IPR024350	Hepatitus C virus, Non-structural 5a protein, C-terminal	Domain
A, B	IPR013193	Hepatitis C virus non-structural 5a, 1B domain	Domain
A, B	IPR004109	Hepatitis C virus, NS3 protease	Domain
A, B	IPR049913	Hepatitis C virus, p7 channel	Domain
A, B	IPR002531	Hepatitis C virus, Non-structural protein E2/NS1	Domain
A, B	IPR043504	Peptidase S1, PA clan, chymotrypsin-like fold	Homologous Superfamily
A, B	IPR007094	RNA-directed RNA polymerase, catalytic domain	Domain
A, B	IPR001490	Hepatitis C virus, Non-structural protein NS4b	Domain
C	IPR002522	Hepatitis C virus, Core protein, N-terminal	Domain
C	IPR043128	Reverse transcriptase/Diguanylate cyclase domain	Homologous Superfamily
C	IPR054175	NS3 RNA helicase, C-terminal helical domain	Domain
C	IPR038568	Hepatitis C virus NS5A, 1B domain superfamily	Homologous Superfamily
C	IPR027417	P-loop containing nucleoside triphosphate hydrolase	Homologous Superfamily
C	IPR009003	Peptidase S1, PA clan	Homologous Superfamily
C	IPR001650	Helicase, C-terminal domain-like	Domain
C	IPR014001	Helicase superfamily 1/2, ATP-binding domain	Domain
C	IPR002868	Hepatitis C virus, Non-structural 5a protein	Domain
C	IPR038170	NS5A domain 1a superfamily	Homologous Superfamily
C	IPR002518	Hepatitis C virus, Non-structural protein NS2	Domain
C	IPR013192	Hepatitis C virus, Non-structural 5a protein, domain 1a	Domain
C	IPR002521	Hepatitis C virus, Core protein, C-terminal	Domain
C	IPR042209	Hepatitis C virus non-structural protein NS2, N-terminal domain	Homologous Superfamily
C	IPR000745	Hepatitis C virus, Non-structural protein NS4a	Domain
C	IPR011492	Non-structural protein NS3-like, DEAD box helicase, flavivirus	Domain
C	IPR042205	Hepatitis C virus non-structural protein NS2, C-terminal domain	Homologous Superfamily
C	IPR002166	RNA dependent RNA polymerase, hepatitis C virus	Family
C	IPR002519	Hepatitis C virus, Envelope glycoprotein E1	Domain
C	IPR043502	DNA/RNA polymerase superfamily	Homologous Superfamily
C	IPR044896	Hepatitis C virus core protein, chain A superfamily	Homologous Superfamily
C	IPR024350	Hepatitus C virus, Non-structural 5a protein, C-terminal	Domain
C	IPR013193	Hepatitis C virus non-structural 5a, 1B domain	Domain
C	IPR004109	Hepatitis C virus, NS3 protease	Domain
C	IPR049913	Hepatitis C virus, p7 channel	Domain
C	IPR002531	Hepatitis C virus, Non-structural protein E2/NS1	Domain
C	IPR043504	Peptidase S1, PA clan, chymotrypsin-like fold	Homologous Superfamily
C	IPR007094	RNA-directed RNA polymerase, catalytic domain	Domain
C	IPR001490	Hepatitis C virus, Non-structural protein NS4b	Domain

Protein Modification Annotation

Modified Residue(s)
Chain	Residue(s)	Description
C	ACE	RESID: AA0041 , AA0042 , AA0043 , AA0044 , AA0045 , AA0046 , AA0049 , AA0050 , AA0051 , AA0052 , AA0053 , AA0054 , AA0354 PSI-MOD : N-acetyl-L-alanine MOD:00050 , N-acetyl-L-aspartic acid MOD:00051 , N-acetyl-L-cysteine MOD:00052 , N-acetyl-S-archeol-cysteine MOD:00897 , N-acetyl-L-glutamic acid MOD:00053 , N-acetyl-L-glutamine MOD:00054 , N-acetylglycine MOD:00055 , N-acetyl-L-methionine MOD:00058 , N-acetyl-L-proline MOD:00059 , N-acetyl-L-serine MOD:00060 , N,O-diacetylated L-serine MOD:00648 , N-acetyl-L-threonine MOD:00061 , N-acetyl-L-tyrosine MOD:00062 , N-acetyl-L-valine MOD:00063 , N2-acetyl-L-arginine MOD:00359