Target Information
| Target General Information | Top | |||||
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| Target ID |
T57654
(Former ID: TTDI01738)
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| Target Name |
Influenza Polymerase basic protein 2 (Influ PB2)
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| Synonyms |
RNA-directed RNA polymerase subunit P3; Polymerase basic protein 2
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| Gene Name |
Influ PB2
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Influenza [ICD-11: 1E30-1E32] | |||||
| Function |
Plays an essential role in transcription initiation and cap-stealing mechanism, in which cellular capped pre-mRNAs are used to generate primers for viral transcription. Recognizes and binds the 7-methylguanosine-containing cap of the target pre-RNA which is subsequently cleaved after 10-13 nucleotides by the viral protein PA. Plays a role in the initiation of the viral genome replication and modulates the activity of the ribonucleoprotein (RNP) complex. In addition, participates in the inhibition of type I interferon induction through interaction with and inhibition of the host mitochondrial antiviral signaling protein MAVS.
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| UniProt ID | ||||||
| Sequence |
MERIKELRNLMSQSRTREILTKTTVDHMAIIKKYTSGRQEKNPALRMKWMMAMKYPITAD
KRITEMIPERNEQGQTLWSKMNDAGSDRVMVSPLAVTWWNRNGPITNTVHYPKIYKTYFE RVERLKHGTFGPVHFRNQVKIRRRVDINPGHADLSAKEAQDVIMEVVFPNEVGARILTSE SQLTITKEKKEELQDCKISPLMVAYMLERELVRKTRFLPVAGGTSSVYIEVLHLTQGTCW EQMYTPGGEVRNDDVDQSLIIAARNIVRRAAVSADPLASLLEMCHSTQIGGIRMVDILRQ NPTEEQAVDICKAAMGLRISSSFSFGGFTFKRTSGSSVKREEEVLTGNLQTLKIRVHEGY EEFTMVGRRATAILRKATRRLIQLIVSGRDEQSIAEAIIVAMVFSQEDCMIKAVRGDLNF VNRANQRLNPMHQLLRHFQKDAKVLFQNWGVEPIDNVMGMIGILPDMTPSIEMSMRGVRI SKMGVDEYSSTERVVVSIDRFLRIRDQRGNVLLSPEEVSETQGTEKLTITYSSSMMWEIN GPESVLVNTYQWIIRNWETVKIQWSQNPTMLYNKMEFEPFQSLVPKAIRGQYSGFVRTLF QQMRDVLGTFDTAQIIKLLPFAAAPPKQSRMQFSSFTVNVRGSGMRILVRGNSPVFNYNK ATKRLTVLGKDAGTLTEDPDEGTAGVESAVLRGFLILGKEDKRYGPALSINELSNLAKGE KANVLIGQGDVVLVMKRKRDSSILTDSQTATKRIRMAIN Click to Show/Hide
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| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | VX-787 | Drug Info | Phase 3 | Influenza A virus infection | [2] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 1 Inhibitor drugs | + | ||||
| 1 | VX-787 | Drug Info | [1] | |||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: 1,4-Butanediol | Ligand Info | |||||
| Structure Description | Crystal structure of the cap-binding domain of polymerase basic protein 2 from influenza virus A/Puerto Rico/8/34(h1n1) | PDB:4ENF | ||||
| Method | X-ray diffraction | Resolution | 1.32 Å | Mutation | No | [3] |
| PDB Sequence |
SSSFSFGGFT
329 FKRTSGSSVK339 REEEVLTGNL349 QTLKIRVHEG359 YEEFTMVGRR369 ATAILRKATR 379 RLIQLIVSGR389 DEQSIAEAII399 VAMVFSQEDC409 MIKAVRGDLN419 FVNRANQRLN 429 PMHQLLRHFQ439 KDAKVLFQNW449 GVEPIDNVMG459 MIGILPDMTP469 SIEMSMRGVR 479 ISKM
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| Ligand Name: 7N-Methyl-8-hydroguanosine-5'-triphosphate | Ligand Info | |||||
| Structure Description | P453H/I471T mutant of PB2 middle domain from influenza virus A/Puerto Rico/8/34(H1N1) with m7GTP | PDB:3WI1 | ||||
| Method | X-ray diffraction | Resolution | 1.93 Å | Mutation | Yes | [4] |
| PDB Sequence |
SFSFGGFTFK
331 RTSGSSVKRE341 EEVLTGNLQT351 LKIRVHEGYE361 EFTMVGRRAT371 AILRKATRRL 381 IQLIVSGRDE391 QSIAEAIIVA401 MVFSQEDCMI411 KAVRGDLNFV421 NRANQRLNPM 431 HQLLRHFQKD441 AKVLFQNWGV451 EHIDNVMGMI461 GILPDMTPST471 EMSMRGVRIS 481 KM
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Similarity Proteins
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There is no similarity protein (E value < 0.005) for this target
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| Chemical Structure based Activity Landscape of Target | Top |
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| References | Top | |||||
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| REF 1 | Discovery of a novel, first-in-class, orally bioavailable azaindole inhibitor (VX-787) of influenza PB2. J Med Chem. 2014 Aug 14;57(15):6668-78. | |||||
| REF 2 | ClinicalTrials.gov (NCT03376321) A Study to Evaluate the Efficacy and Safety of Pimodivir in Combination With the Standard-of-Care Treatment in Adolescent, Adult, and Elderly Hospitalized Participants With Influenza A Infection. U.S. National Institutes of Health. | |||||
| REF 3 | Structural and functional characterization of K339T substitution identified in the PB2 subunit cap-binding pocket of influenza A virus. J Biol Chem. 2013 Apr 19;288(16):11013-23. | |||||
| REF 4 | Conformational polymorphism of m7GTP in crystal structure of the PB2 middle domain from human influenza A virus. PLoS One. 2013 Nov 29;8(11):e82020. | |||||
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