NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|22219303]
View 

Chain A, Replicase, hydrolase domain

Protein Classification

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

 Name Accession Description Interval E-value
alphaCoV_Nsp5_Mpro cd21665
alphacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily ...
 3-298 0e+00

alphacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily contains the coronavirus (CoV) non-structural protein 5 (Nsp5) also called the Main protease (Mpro), or 3C-like protease (3CLpro), found in alphacoronaviruses. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Mpro/Nsp5 is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. These enzymes belong to the MEROPS peptidase C30 family, where the active site residues His and Cys form a catalytic dyad. The structures of Mpro/Nsp5 consist of three domains with the first two containing anti-parallel beta barrels and the third consisting of an arrangement of alpha-helices. The catalytic residues are found in a cleft between the first two domains. Mpro/Nsp5 requires a Gln residue in the P1 position of the substrate and space for only small amino-acid residues such as Gly, Ala, or Ser in the P1' position; since there is no known human protease with a specificity for Gln at the cleavage site of the substrate, these viral proteases are suitable targets for the development of antiviral drugs.


:

Pssm-ID: 394886  Cd Length: 296  Bit Score: 571.16  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22219303   3 LRKMAQPSGLVEPCIVRVSYGNNVLNGLWLGDEVICPRHVIASDTTRVINYENEMSSVRLHNFSVSKNNVFLGVVSARYK 82
Cdd:cd21665   1 LRKMAQPSGVVEKCVVRVSYGNMVLNGLWLGDTVYCPRHVIASDTTSTIDYDHEYSLMRLHNFSISVGNVFLGVVGVTMR 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22219303  83 GVNLVLKVNQVNPNTPEHKFKSIKAGESFNILACYEGCPGSVYGVNMRSQGTIKGSFIAGTCGSVGYVLENGILYFVYMH 162
Cdd:cd21665  81 GALLVIKVNQNNVNTPKYTFRTLKPGDSFNILACYDGVPSGVYGVNMRTNYTIKGSFINGACGSPGYNLNNGTVEFCYMH 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22219303 163 HLELGNGSHVGSNFEGEMYGGYEDQPSMQLEGTNVMSSDNVVAFLYAALINGERWFVTNTSMSLESYNTWAKTNSFTELS 242
Cdd:cd21665 161 QLELGSGCHVGSDLDGVMYGGYEDQPTLQVEGANVLVTENVVAFLYAALLNGCNWWLSSDRVTVEAFNEWAVANGFTTVS 240

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 22219303 243 STDAFSMLAAKTGQSVEKLLDSIVRLNKGFGGRTILSYGSLCDEFTPTEVIRQMYG 298
Cdd:cd21665 241 STDCFSILAAKTGVDVERLLAAIQRLSKGFGGKTILGYTSLTDEFTLSEVIKQMYG 296
 
Name Accession Description Interval E-value
alphaCoV_Nsp5_Mpro cd21665
alphacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily ...
 3-298 0e+00

alphacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily contains the coronavirus (CoV) non-structural protein 5 (Nsp5) also called the Main protease (Mpro), or 3C-like protease (3CLpro), found in alphacoronaviruses. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Mpro/Nsp5 is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. These enzymes belong to the MEROPS peptidase C30 family, where the active site residues His and Cys form a catalytic dyad. The structures of Mpro/Nsp5 consist of three domains with the first two containing anti-parallel beta barrels and the third consisting of an arrangement of alpha-helices. The catalytic residues are found in a cleft between the first two domains. Mpro/Nsp5 requires a Gln residue in the P1 position of the substrate and space for only small amino-acid residues such as Gly, Ala, or Ser in the P1' position; since there is no known human protease with a specificity for Gln at the cleavage site of the substrate, these viral proteases are suitable targets for the development of antiviral drugs.


Pssm-ID: 394886  Cd Length: 296  Bit Score: 571.16  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22219303   3 LRKMAQPSGLVEPCIVRVSYGNNVLNGLWLGDEVICPRHVIASDTTRVINYENEMSSVRLHNFSVSKNNVFLGVVSARYK 82
Cdd:cd21665   1 LRKMAQPSGVVEKCVVRVSYGNMVLNGLWLGDTVYCPRHVIASDTTSTIDYDHEYSLMRLHNFSISVGNVFLGVVGVTMR 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22219303  83 GVNLVLKVNQVNPNTPEHKFKSIKAGESFNILACYEGCPGSVYGVNMRSQGTIKGSFIAGTCGSVGYVLENGILYFVYMH 162
Cdd:cd21665  81 GALLVIKVNQNNVNTPKYTFRTLKPGDSFNILACYDGVPSGVYGVNMRTNYTIKGSFINGACGSPGYNLNNGTVEFCYMH 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22219303 163 HLELGNGSHVGSNFEGEMYGGYEDQPSMQLEGTNVMSSDNVVAFLYAALINGERWFVTNTSMSLESYNTWAKTNSFTELS 242
Cdd:cd21665 161 QLELGSGCHVGSDLDGVMYGGYEDQPTLQVEGANVLVTENVVAFLYAALLNGCNWWLSSDRVTVEAFNEWAVANGFTTVS 240

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 22219303 243 STDAFSMLAAKTGQSVEKLLDSIVRLNKGFGGRTILSYGSLCDEFTPTEVIRQMYG 298
Cdd:cd21665 241 STDCFSILAAKTGVDVERLLAAIQRLSKGFGGKTILGYTSLTDEFTLSEVIKQMYG 296
Peptidase_C30 pfam05409
Coronavirus endopeptidase C30; This Coronavirus (CoV) domain, peptidase C30, is also known as ...
 29-302 1.93e-177

Coronavirus endopeptidase C30; This Coronavirus (CoV) domain, peptidase C30, is also known as 3C-like proteinase (3CL-pro), or CoV main protease (M-pro) domain. CoV M-pro is a dimer where each subunit is composed of three domains I, II and III,,. Domains I and II consist of six-stranded antiparallel beta barrels and together resemble the architecture of chymotrypsin, and of picornaviruses 3C proteinases. The substrate-binding site is located in a cleft between these two domains. The catalytic site is situated at the centre of the cleft. A long loop connects domain II to the C-terminal domain (domain III). This latter domain has been implicated in the proteolytic activity of M-pro. In the active site of M-pro, Cys and His form a catalytic dyad,.


Pssm-ID: 398852  Cd Length: 274  Bit Score: 490.80  E-value: 1.93e-177
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22219303    29 GLWLGDEVICPRHVIASDTTRVINYENEMSSVRLHNFSVSKNNVFLGVVSARYKGVNLVLKVNQVNPNTPEHKFKSIKAG 108
Cdd:pfam05409   1 GLWLGDTVYCPRHVIGSFTGMLPQYEHLLSIARNHDFCVVSGGVQLTVVSAKMQGAILVLKVHTNNPNTPKYKFVRLKPG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22219303   109 ESFNILACYEGCPGSVYGVNMRSQGTIKGSFIAGTCGSVGYVLENGILYFVYMHHLELGNGSHVGSNFEGEMYGGYEDQP 188
Cdd:pfam05409  81 ESFTILAAYDGCPQGVYHVTMRSNHTIKGSFLNGACGSVGYNLKGGTVCFVYMHHLELPNGSHTGTDLEGVFYGPYVDEE 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22219303   189 SMQLEGTNVMSSDNVVAFLYAALINGERWFVTNTSMSLESYNTWAKTNSFTELSSTDAFSMLAAKTGQSVEKLLDSIVRL 268
Cdd:pfam05409 161 VAQLEGTDQTYTDNVVAWLYAAIINGPRWFLASTTVSLEDFNAWAMTNGFTPFPCEDAILGLAAKTGVSVERLLAAIKVL 240

                         250       260       270
                  ....*....|....*....|....*....|....
gi 22219303   269 NKGFGGRTILSYGSLCDEFTPTEVIRQMYGVNLQ 302
Cdd:pfam05409 241 NNGFGGRTILGSPSLEDEFTPEDVYNQMAGVTLQ 274
 
Name Accession Description Interval E-value
alphaCoV_Nsp5_Mpro cd21665
alphacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily ...
 3-298 0e+00

alphacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily contains the coronavirus (CoV) non-structural protein 5 (Nsp5) also called the Main protease (Mpro), or 3C-like protease (3CLpro), found in alphacoronaviruses. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Mpro/Nsp5 is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. These enzymes belong to the MEROPS peptidase C30 family, where the active site residues His and Cys form a catalytic dyad. The structures of Mpro/Nsp5 consist of three domains with the first two containing anti-parallel beta barrels and the third consisting of an arrangement of alpha-helices. The catalytic residues are found in a cleft between the first two domains. Mpro/Nsp5 requires a Gln residue in the P1 position of the substrate and space for only small amino-acid residues such as Gly, Ala, or Ser in the P1' position; since there is no known human protease with a specificity for Gln at the cleavage site of the substrate, these viral proteases are suitable targets for the development of antiviral drugs.


Pssm-ID: 394886  Cd Length: 296  Bit Score: 571.16  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22219303   3 LRKMAQPSGLVEPCIVRVSYGNNVLNGLWLGDEVICPRHVIASDTTRVINYENEMSSVRLHNFSVSKNNVFLGVVSARYK 82
Cdd:cd21665   1 LRKMAQPSGVVEKCVVRVSYGNMVLNGLWLGDTVYCPRHVIASDTTSTIDYDHEYSLMRLHNFSISVGNVFLGVVGVTMR 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22219303  83 GVNLVLKVNQVNPNTPEHKFKSIKAGESFNILACYEGCPGSVYGVNMRSQGTIKGSFIAGTCGSVGYVLENGILYFVYMH 162
Cdd:cd21665  81 GALLVIKVNQNNVNTPKYTFRTLKPGDSFNILACYDGVPSGVYGVNMRTNYTIKGSFINGACGSPGYNLNNGTVEFCYMH 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22219303 163 HLELGNGSHVGSNFEGEMYGGYEDQPSMQLEGTNVMSSDNVVAFLYAALINGERWFVTNTSMSLESYNTWAKTNSFTELS 242
Cdd:cd21665 161 QLELGSGCHVGSDLDGVMYGGYEDQPTLQVEGANVLVTENVVAFLYAALLNGCNWWLSSDRVTVEAFNEWAVANGFTTVS 240

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 22219303 243 STDAFSMLAAKTGQSVEKLLDSIVRLNKGFGGRTILSYGSLCDEFTPTEVIRQMYG 298
Cdd:cd21665 241 STDCFSILAAKTGVDVERLLAAIQRLSKGFGGKTILGYTSLTDEFTLSEVIKQMYG 296
Peptidase_C30 pfam05409
Coronavirus endopeptidase C30; This Coronavirus (CoV) domain, peptidase C30, is also known as ...
 29-302 1.93e-177

Coronavirus endopeptidase C30; This Coronavirus (CoV) domain, peptidase C30, is also known as 3C-like proteinase (3CL-pro), or CoV main protease (M-pro) domain. CoV M-pro is a dimer where each subunit is composed of three domains I, II and III,,. Domains I and II consist of six-stranded antiparallel beta barrels and together resemble the architecture of chymotrypsin, and of picornaviruses 3C proteinases. The substrate-binding site is located in a cleft between these two domains. The catalytic site is situated at the centre of the cleft. A long loop connects domain II to the C-terminal domain (domain III). This latter domain has been implicated in the proteolytic activity of M-pro. In the active site of M-pro, Cys and His form a catalytic dyad,.


Pssm-ID: 398852  Cd Length: 274  Bit Score: 490.80  E-value: 1.93e-177
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22219303    29 GLWLGDEVICPRHVIASDTTRVINYENEMSSVRLHNFSVSKNNVFLGVVSARYKGVNLVLKVNQVNPNTPEHKFKSIKAG 108
Cdd:pfam05409   1 GLWLGDTVYCPRHVIGSFTGMLPQYEHLLSIARNHDFCVVSGGVQLTVVSAKMQGAILVLKVHTNNPNTPKYKFVRLKPG 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22219303   109 ESFNILACYEGCPGSVYGVNMRSQGTIKGSFIAGTCGSVGYVLENGILYFVYMHHLELGNGSHVGSNFEGEMYGGYEDQP 188
Cdd:pfam05409  81 ESFTILAAYDGCPQGVYHVTMRSNHTIKGSFLNGACGSVGYNLKGGTVCFVYMHHLELPNGSHTGTDLEGVFYGPYVDEE 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22219303   189 SMQLEGTNVMSSDNVVAFLYAALINGERWFVTNTSMSLESYNTWAKTNSFTELSSTDAFSMLAAKTGQSVEKLLDSIVRL 268
Cdd:pfam05409 161 VAQLEGTDQTYTDNVVAWLYAAIINGPRWFLASTTVSLEDFNAWAMTNGFTPFPCEDAILGLAAKTGVSVERLLAAIKVL 240

                         250       260       270
                  ....*....|....*....|....*....|....
gi 22219303   269 NKGFGGRTILSYGSLCDEFTPTEVIRQMYGVNLQ 302
Cdd:pfam05409 241 NNGFGGRTILGSPSLEDEFTPEDVYNQMAGVTLQ 274
CoV_Nsp5_Mpro cd21646
coronavirus non-structural protein 5, also called Main protease (Mpro); This family contains ...
 4-295 2.01e-155

coronavirus non-structural protein 5, also called Main protease (Mpro); This family contains the coronavirus (CoV) non-structural protein 5 (Nsp5) also called the Main protease (Mpro), or 3C-like protease (3CLpro). CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Mpro/Nsp5 is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. These enzymes belong to the MEROPS peptidase C30 family, where the active site residues His and Cys form a catalytic dyad. The structures of Mpro/Nsp5 consist of three domains with the first two containing anti-parallel beta barrels and the third consisting of an arrangement of alpha-helices. The catalytic residues are found in a cleft between the first two domains. Mpro/Nsp5 requires a Gln residue in the P1 position of the substrate and space for only small amino-acid residues such as Gly, Ala, or Ser in the P1' position; since there is no known human protease with a specificity for Gln at the cleavage site of the substrate, these viral proteases are suitable targets for the development of antiviral drugs.


Pssm-ID: 394885  Cd Length: 292  Bit Score: 435.70  E-value: 2.01e-155
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22219303   4 RKMAQPSGLVEPCIVRVSYGNNVLNGLWLGDEVICPRHVIASDTTRVINYENEMSSVRLHNFSVSKNNVFLGVVSARYKG 83
Cdd:cd21646   1 KKMAQPSGKVERCMVSVTYGSTTLNGLWLDDTVYCPRHVICKSTTSGPDYDDLLSRARNHNFSVQSGGVQLRVVGVTMQG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22219303  84 VNLVLKVNQVNPNTPEHKFKSIKAGESFNILACYEGCPGSVYGVNMRSQGTIKGSFIAGTCGSVGYVLENGILYFVYMHH 163
Cdd:cd21646  81 ALLRLKVDTSNPHTPKYKFVTVKPGDSFTILACYNGSPSGVYGVNMRSNYTIKGSFLNGACGSVGYNIDGGTVEFCYMHH 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22219303 164 LELGNGSHVGSNFEGEMYGGYEDQPSMQLEGTNVMSSDNVVAFLYAALINGERWFVTNTSMSLESYNTWAKTNSFTELSS 243
Cdd:cd21646 161 LELPNGCHTGTDLTGKFYGPYVDQQVAQVEGADTLITDNVVAWLYAAIINGDRWWLNSSRTTVNDFNEWAMANGFTPVSQ 240

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|..
gi 22219303 244 TDAFSMLAAKTGQSVEKLLDSIVRLNKGFGGRTILSYGSLCDEFTPTEVIRQ 295
Cdd:cd21646 241 VDCLSILAAKTGVSVERLLAAIQQLHQNFGGKQILGSTSLEDEFTPEDVVRQ 292
betaCoV_Nsp5_Mpro cd21666
betacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily ...
 4-296 9.08e-126

betacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily contains the coronavirus (CoV) non-structural protein 5 (Nsp5) also called the Main protease (Mpro), or 3C-like protease (3CLpro), found in betacoronaviruses. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Mpro/Nsp5 is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. These enzymes belong to the MEROPS peptidase C30 family, where the active site residues His and Cys form a catalytic dyad. The structures of Mpro/Nsp5 consist of three domains with the first two containing anti-parallel beta barrels and the third consisting of an arrangement of alpha-helices. The catalytic residues are found in a cleft between the first two domains. Mpro requires a Gln residue in the P1 position of the substrate and space for only small amino-acid residues such as Gly, Ala, or Ser in the P1' position; since there is no known human protease with a specificity for Gln at the cleavage site of the substrate, these viral proteases are suitable targets for the development of antiviral drugs.


Pssm-ID: 394887  Cd Length: 297  Bit Score: 360.95  E-value: 9.08e-126
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22219303   4 RKMAQPSGLVEPCIVRVSYGNNVLNGLWLGDEVICPRHVIASDTTRVI-NYENEMSSVRLHNFSVSKNNVFLGVVSARYK 82
Cdd:cd21666   1 RKMAFPSGKVEGCMVQVTCGTMTLNGLWLDDTVYCPRHVICTAEDMLNpNYEDLLIRKTNHSFLVQAGNVQLRVIGHSMQ 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22219303  83 GVNLVLKVNQVNPNTPEHKFKSIKAGESFNILACYEGCPGSVYGVNMRSQGTIKGSFIAGTCGSVGYVLENGILYFVYMH 162
Cdd:cd21666  81 GCLLRLTVDTSNPKTPKYKFVRVKPGQTFSVLACYNGSPSGVYQCAMRPNHTIKGSFLCGSCGSVGYNIDGDCVSFCYMH 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22219303 163 HLELGNGSHVGSNFEGEMYGGYEDQPSMQLEGTNVMSSDNVVAFLYAALINGERWFVTNTSMSLESYNTWAKTNSFTELS 242
Cdd:cd21666 161 QMELPTGVHTGTDLEGKFYGPFVDRQTAQAAGTDTTITLNVLAWLYAAVLNGDRWFVNRFTTTLNDFNLWAMKYNYEPLT 240

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 22219303 243 --STDAFSMLAAKTGQSVEKLLDSIVRLNKGFG-GRTILSYGSLCDEFTPTEVIRQM 296
Cdd:cd21666 241 qdHVDILDPLAAQTGIAVEDMLAALKELLQGGMqGRTILGSTILEDEFTPFDVVRQC 297
gammaCoV_Nsp5_Mpro cd21667
gammacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily ...
 2-302 4.66e-89

gammacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily contains the coronavirus (CoV) non-structural protein 5 (Nsp5) also called the Main protease (Mpro), or 3C-like protease (3CLpro), found in gammacoronaviruses. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Mpro/Nsp5 is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. These enzymes belong to the MEROPS peptidase C30 family, where the active site residues His and Cys form a catalytic dyad. The structures of Mpro/Nsp5 consist of three domains with the first two containing anti-parallel beta barrels and the third consisting of an arrangement of alpha-helices. The catalytic residues are found in a cleft between the first two domains. Mpro/Nsp5 requires a Gln residue in the P1 position of the substrate and space for only small amino-acid residues such as Gly, Ala, or Ser in the P1' position; since there is no known human protease with a specificity for Gln at the cleavage site of the substrate, these viral proteases are suitable targets for the development of antiviral drugs.


Pssm-ID: 394888  Cd Length: 306  Bit Score: 267.81  E-value: 4.66e-89
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22219303   2 GLRKMAQPSGLVEPCIVRVSYGNNVLNGLWLGDEVICPRHVIASDTTRviNYENEMSSVRLHNFSV-SKNNVFLGVVSAR 80
Cdd:cd21667   1 GFKKLVSPSSAVEKCIVSVSYRGNNLNGLWLGDSIYCPRHVLGKFSGD--QWQDVLNLANNHEFEVvTQNGVTLNVVSRR 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22219303  81 YKGVNLVLKVNQVNPNTPEHKFKSIKAGESFNILACYEGCPGSVYGVNMRSQGTIKGSFIAGTCGSVGYVLENGILYFVY 160
Cdd:cd21667  79 LKGAVLILQTAVANANTPKYKFVKANCGDSFTIACSYGGTVVGLYPVTMRSNGTIRASFLAGACGSVGFNIEKGVVNFFY 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22219303 161 MHHLELGNGSHVGSNFEGEMYGGYEDQPSMQLEGTNVMSSDNVVAFLYAALINGE-------RWfVTNTSMSLESYNTWA 233
Cdd:cd21667 159 MHHLELPNALHTGTDLMGEFYGGYVDEEVAQRVPPDNLVTNNIVAWLYAAIISVKessfslpKW-LESTTVSVEDYNKWA 237

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 22219303 234 KTNSFTELSSTDAFSMLAAKTGQSVEKLLDSIVRLNKGFGGRTILSYGSLCDEFTPTEVIRQMYGVNLQ 302
Cdd:cd21667 238 SDNGFTPFSTSTAITKLSAITGVDVCKLLRTIMVKSAQWGSDPILGQYNFEDELTPESVFNQVGGVRLQ 306
deltaCoV_Nsp5_Mpro cd21668
deltacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily ...
 1-295 3.02e-65

deltacoronavirus non-structural protein 5, also called Main protease (Mpro); This subfamily contains the coronavirus (CoV) non-structural protein 5 (Nsp5) also called the Main protease (Mpro), or 3C-like protease (3CLpro), found in deltacoronaviruses. CoVs utilize a multi-subunit replication/transcription machinery. A set of non-structural proteins (Nsps) generated as cleavage products of the ORF1a and ORF1ab viral polyproteins assemble to facilitate viral replication and transcription. Mpro/Nsp5 is a key enzyme in this process, making it a high value target for the development of anti-coronavirus therapeutics. These enzymes belong to the MEROPS peptidase C30 family, where the active site residues His and Cys form a catalytic dyad. The structures of Mpro/Nsp5 consist of three domains with the first two containing anti-parallel beta barrels and the third consisting of an arrangement of alpha-helices. The catalytic residues are found in a cleft between the first two domains. Mpro/Nsp5 requires a Gln residue in the P1 position of the substrate and space for only small amino-acid residues such as Gly, Ala, or Ser in the P1' position; since there is no known human protease with a specificity for Gln at the cleavage site of the substrate, these viral proteases are suitable targets for the development of antiviral drugs.


Pssm-ID: 394889  Cd Length: 302  Bit Score: 206.97  E-value: 3.02e-65
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22219303   1 SGLRKMAQPSGLVEPCIVRVSYGNNVLNGLWLGDEVICPRHVIASDTTRviNYENEMSSVRLHNFSVSKNN--VFLGVVS 78
Cdd:cd21668   2 AGIKILLHPSGVVERCMVSVTYNGSTLNGIWLHNVVYCPRHVIGKYTGS--QWQDMVSIADCRDFVIFCPTqgIQLTVQS 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22219303  79 ARYKGVNLVLKVNQVNPNTPEHKFKSIKAGESFNILACYEGCPGSVYGVNMRSQGTIKGSFIAGTCGSVGYVLENGILYF 158
Cdd:cd21668  80 VKMVGAVLQLTVHTKNLHTPDYEFERATPGSSMTIACAYDGIVRNVYHVVLQTNNLIYASFLNGACGSVGYTLKGKTLLL 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 22219303 159 VYMHHLELGNGSHVGSNFEGEMYGGYEDQPSMQLEGTNVMSSDNVVAFLYAAL--INGERWFVTNTSMSLESYNTWAKTN 236
Cdd:cd21668 160 HYMHHLEFNNKTHGGTDLHGHFYGPYVDEEVAQHQTAFQYYTDNVVAQIYAHLltIDAKPKWLASQEISVEDFNEWAANN 239

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 22219303 237 SFT----ELSSTDAFSMLAAKTGQSVEKLLDSIVRLNKGFGGRTILSYGSLCDEFTPTEVIRQ 295
Cdd:cd21668 240 SFAnfpcESSNMAYLEGLAQTTKVSVGRVLNTIIQLTLNRGGALIMGKPDFECDWTPEMVYNQ 302
alphaCoV-Nsp6 cd21558
alphacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host ...
 287-302 1.55e-03

alphacoronavirus non-structural protein 6; Coronaviruses (CoV) redirect and rearrange host cell membranes as part of the viral genome replication and transcription machinery; they induce the formation of double-membrane vesicles in infected cells. CoV non-structural protein 6 (Nsp6), a transmembrane-containing protein, together with Nsp3 and Nsp4, have the ability to induce double-membrane vesicles that are similar to those observed in severe acute respiratory syndrome (SARS) coronavirus-infected cells. By itself, Nsp6 can generate autophagosomes from the endoplasmic reticulum. Autophagosomes are normally generated as a cellular response to starvation to carry cellular organelles and long-lived proteins to lysosomes for degradation. Degradation through autophagy may provide an innate defense against virus infection, or conversely, autophagosomes can promote infection by facilitating the assembly of replicase proteins. In addition to initiating autophagosome formation, Nsp6 also limits autophagosome expansion regardless of how they were induced, i.e. whether they were induced directly by Nsp6, or indirectly by starvation or chemical inhibition of MTOR signaling. This may favor coronavirus infection by compromising the ability of autophagosomes to deliver viral components to lysosomes for degradation.


Pssm-ID: 394844  Cd Length: 293  Bit Score: 39.49  E-value: 1.55e-03
                        10
                ....*....|....*.
gi 22219303 287 FTPTEVIRQMYGVNLQ 302
Cdd:cd21558   1 FTTSEVIKQMYGVNLQ 16
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH