Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T42337
(Former ID: TTDI03371)
|
|||||
| Target Name |
Methionyl aminopeptidase 1 (METAP1)
|
|||||
| Synonyms |
Peptidase M 1; Methionine aminopeptidase 1; MetAP 1; MAP 1; KIAA0094
Click to Show/Hide
|
|||||
| Gene Name |
METAP1
|
|||||
| Target Type |
Literature-reported target
|
[1] | ||||
| Function |
Cotranslationally removes the N-terminal methionine from nascent proteins. The N-terminal methionine is often cleaved when the second residue in the primary sequence is small and uncharged (Met-Ala-, Cys, Gly, Pro, Ser, Thr, or Val). Required for normal progression through the cell cycle.
Click to Show/Hide
|
|||||
| UniProt ID | ||||||
| EC Number |
EC 3.4.11.18
|
|||||
| Sequence |
MAAVETRVCETDGCSSEAKLQCPTCIKLGIQGSYFCSQECFKGSWATHKLLHKKAKDEKA
KREVSSWTVEGDINTDPWAGYRYTGKLRPHYPLMPTRPVPSYIQRPDYADHPLGMSESEQ ALKGTSQIKLLSSEDIEGMRLVCRLAREVLDVAAGMIKPGVTTEEIDHAVHLACIARNCY PSPLNYYNFPKSCCTSVNEVICHGIPDRRPLQEGDIVNVDITLYRNGYHGDLNETFFVGE VDDGARKLVQTTYECLMQAIDAVKPGVRYRELGNIIQKHAQANGFSVVRSYCGHGIHKLF HTAPNVPHYAKNKAVGVMKSGHVFTIEPMICEGGWQDETWPDGWTAVTRDGKRSAQFEHT LLVTDTGCEILTRRLDSARPHFMSQF Click to Show/Hide
|
|||||
| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| ADReCS ID | BADD_A05962 | |||||
| Cell-based Target Expression Variations | Top | |||||
|---|---|---|---|---|---|---|
| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: L-methionine | Ligand Info | |||||
| Structure Description | HsMetAP in complex with methionine | PDB:4U6J | ||||
| Method | X-ray diffraction | Resolution | 1.56 Å | Mutation | No | [2] |
| PDB Sequence |
YRYTGKLRPH
99 YPLMPTRPVP109 SYIQRPDYAD119 HPLGMSESEQ129 ALKGTSQIKL139 LSSEDIEGMR 149 LVCRLAREVL159 DVAAGMIKPG169 VTTEEIDHAV179 HLACIARNCY189 PSPLNYYNFP 199 KSCCTSVNEV209 ICHGIPDRRP219 LQEGDIVNVD229 ITLYRNGYHG239 DLNETFFVGE 249 VDDGARKLVQ259 TTYECLMQAI269 DAVKPGVRYR279 ELGNIIQKHA289 QANGFSVVRS 299 YCGHGIHKLF309 HTAPNVPHYA319 KNKAVGVMKS329 GHVFTIEPMI339 CEGGWQDETW 349 PDGWTAVTRD359 GKRSAQFEHT369 LLVTDTGCEI379 LTRRLDSARP389 HFMS |
|||||
|
|
||||||
| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: 4-[4-(4-Methoxyphenyl)piperazin-1-Yl]-2-(Pyridin-2-Yl)quinazoline | Ligand Info | |||||
| Structure Description | Human Methionine Aminopeptidase in complex with FZ1: Pyridinylquinazolines Selectively Inhibit Human Methionine Aminopeptidase-1 | PDB:4IU6 | ||||
| Method | X-ray diffraction | Resolution | 1.90 Å | Mutation | No | [1] |
| PDB Sequence |
YRYTGKLRPH
99 YPLMPTRPVP109 SYIQRPDYAD119 HPLGMSESEQ129 ALKGTSQIKL139 LSSEDIEGMR 149 LVCRLAREVL159 DVAAGMIKPG169 VTTEEIDHAV179 HLACIARNCY189 PSPLNYYNFP 199 KSCCTSVNEV209 ICHGIPDRRP219 LQEGDIVNVD229 ITLYRNGYHG239 DLNETFFVGE 249 VDDGARKLVQ259 TTYECLMQAI269 DAVKPGVRYR279 ELGNIIQKHA289 QANGFSVVRS 299 YCGHGIHKLF309 HTAPNVPHYA319 KNKAVGVMKS329 GHVFTIEPMI339 CEGGWQDETW 349 PDGWTAVTRD359 GKRSAQFEHT369 LLVTDTGCEI379 LTRRLDSARP389 HFMS |
|||||
|
|
||||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
|---|---|
|
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 Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Biological Network Descriptors
|
|
|
There is no similarity protein (E value < 0.005) for this target
|
|
Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
|
| Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
|---|---|---|---|---|---|
| Closeness centrality | 1.07E-04 | Radiality | 3.98E-03 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 1.00E+00 | Topological coefficient | . | Eccentricity | 1 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
|---|---|
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Pyridinylquinazolines selectively inhibit human methionine aminopeptidase-1 in cells. J Med Chem. 2013 May 23;56(10):3996-4016. | |||||
| REF 2 | Identification of the molecular basis of inhibitor selectivity between the human and streptococcal type I methionine aminopeptidases. J Med Chem. 2015 Mar 12;58(5):2350-7. | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.