Target Information
Target General Information | Top | |||||
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Target ID |
T17248
(Former ID: TTDS00347)
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Target Name |
Measles virus Fusion glycoprotein (MeV F)
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Synonyms |
Measles virus fusion protein; MV fusion protein; Fusion protein
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Gene Name |
MeV F
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 5 Target-related Diseases | + | ||||
1 | Metastatic tumour [ICD-11: 2D50-2E2Z] | |||||
2 | Multiple sclerosis [ICD-11: 8A40] | |||||
3 | Pregnancy/childbirth/puerperium maternal infection [ICD-11: JB63] | |||||
4 | Acute diabete complication [ICD-11: 5A2Y] | |||||
5 | Type 2 diabetes mellitus [ICD-11: 5A11] | |||||
Function |
Class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and plasma cell membrane fusion,the heptad repeat (HR) regions assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C- terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and plasma cell membranes. Directs fusion of viral and cellular membranes leading to delivery of the nucleocapsid into the cytoplasm. This fusion is pH independent and occurs directly at the outer cell membrane. The trimer of F1-F2 (F protein) probably interacts with HN at the virion surface. Upon HN binding to its cellular receptor, the hydrophobic fusion peptide is unmasked and interacts with the cellular membrane, inducing the fusion between cell and virion membranes. Later in infection, F proteins expressed at the plasma membrane of infected cells could mediate fusion with adjacent cells to form syncytia, a cytopathic effect that could lead to tissue necrosis.
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BioChemical Class |
Paramyxoviruses fusion glycoprotein
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UniProt ID | ||||||
Sequence |
MGLKVNVSAIFMAVLLTLQTPTGQIHWGNLSKIGVVGIGSASYKVMTRSSHQSLVIKLMP
NITLLNNCTRVEIAEYRRLLRTVLEPIRDALNAMTQNIRPVQSVASSRRHKRFAGVVLAG AALGVATAAQITAGIALHQSMLNSQAIDNLRASLETTNQAIEAIRQAGQEMILAVQGVQD YINNELIPSMNQLSCDLIGQKLGLKLLRYYTEILSLFGPSLRDPISAEISIQALSYALGG DINKVLEKLGYSGGDLLGILESRGIKARITHVDTESYFIVLSIAYPTLSEIKGVIVHRLE GVSYNIGSQEWYTTVPKYVATQGYLISNFDESSCTFMPEGTVCSQNALYPMSPLLQECLR GSTKSCARTLVSGSFGNRFILSQGNLIANCASILCKCYTTGTIINQDPDKILTYIAADHC PVVEVNGVTIQVGSRRYPDAVYLHRIDLGPPISLERLDVGTNLGNAIAKLEDAKELLESS DQILRSMKGLSSTSIVYILIAVCLGGLIGIPALICCCRGRCNKKGEQVGMSRPGLKPDLT GTSKSYVRSL Click to Show/Hide
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Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 4 Clinical Trial Drugs | + | ||||
1 | MLN1202 | Drug Info | Phase 2 | Multiple sclerosis | [2] | |
2 | TTP889 | Drug Info | Phase 2 | Blood forming organ disorder | [3] | |
3 | AC 165198 | Drug Info | Phase 1 | Diabetic complication | [4] | |
4 | AMG 876 | Drug Info | Phase 1 | Type-2 diabetes | [5] | |
Mode of Action | [+] 2 Modes of Action | + | ||||
Inhibitor | [+] 2 Inhibitor drugs | + | ||||
1 | MLN1202 | Drug Info | [1] | |||
2 | TTP889 | Drug Info | [1] | |||
Modulator | [+] 2 Modulator drugs | + | ||||
1 | AC 165198 | Drug Info | [6] | |||
2 | AMG 876 | Drug Info | [7] |
Drug Binding Sites of Target | Top | |||||
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Ligand Name: 4-Nitro-2-[(phenylacetyl)amino]benzamide | Ligand Info | |||||
Structure Description | Crystal structure of the prefusion form of measles virus fusion protein in complex with a fusion inhibitor compound (AS-48) | PDB:5YZC | ||||
Method | X-ray diffraction | Resolution | 2.33 Å | Mutation | No | [8] |
PDB Sequence |
GVVLAGAALG
124 VATAAQITAG134 IALHQSMLNS144 QAIDNLRASL154 ETTNQAIEAI164 RQAGQEMILA 174 VQGVQDYINN184 ELIPSMNQLS194 CDLIGQKLGL204 KLLRYYTEIL214 SLFGPSLRDP 224 ISAEISIQAL234 SYALGGDINK244 VLEKLGYSGG254 DLLGILESRG264 IKARITHVDT 274 ESYFIVLSIA284 YPTLSEIKGV294 IVHRLEGVSY304 NIGSQEWYTT314 VPKYVATQGY 324 LISNFDESSC334 TFMPEGTVCS344 QNALYPMSPL354 LQECLRGSTK364 SCARTLVSGS 374 FGNRFILSQG384 NLIANCASIL394 CKCYTTGTII404 NQDPDKILTY414 IAADHCPVVE 424 VNGVTIQVGS434 RRYPDAVYLH444 RIDLGPPISL454 ERLDVGTNLG464 NAIAKLEDAK 474 ELLESSD
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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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References | Top | |||||
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REF 1 | Emerging drugs for respiratory syncytial virus infection. Expert Opin Emerg Drugs. 2009 Jun;14(2):207-17. | |||||
REF 2 | Emerging drugs for the therapy of primary and post essential thrombocythemia, post polycythemia vera myelofibrosis. Expert Opin Emerg Drugs. 2009 Sep;14(3):471-9. | |||||
REF 3 | Partial factor IXa inhibition with TTP889 for prevention of venous thromboembolism: an exploratory study. J Thromb Haemost. 2008 Mar;6(3):457-63. | |||||
REF 4 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800030890) | |||||
REF 5 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800035526) | |||||
REF 6 | WO patent application no. 2013,1306,83, Xten conjugate compositions and methods of making same. | |||||
REF 7 | Clinical pipeline report, company report or official report of Amgen. | |||||
REF 8 | Structures of the prefusion form of measles virus fusion protein in complex with inhibitors. Proc Natl Acad Sci U S A. 2018 Mar 6;115(10):2496-2501. |
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