Target Information
| Target General Information | Top | |||||
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| Target ID |
T70036
(Former ID: TTDR01065)
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| Target Name |
Glutamate carboxypeptidase III (NAALAD2)
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| Synonyms |
NAALADase II; NAALAD2
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| Gene Name |
NAALAD2
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Has N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity. Also exhibits a dipeptidyl-peptidase IV type activity. Inactivate the peptide neurotransmitter N- acetylaspartylglutamate.
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| BioChemical Class |
Peptidase
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| UniProt ID | ||||||
| EC Number |
EC 3.4.17.21
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| Sequence |
MAESRGRLYLWMCLAAALASFLMGFMVGWFIKPLKETTTSVRYHQSIRWKLVSEMKAENI
KSFLRSFTKLPHLAGTEQNFLLAKKIQTQWKKFGLDSAKLVHYDVLLSYPNETNANYISI VDEHETEIFKTSYLEPPPDGYENVTNIVPPYNAFSAQGMPEGDLVYVNYARTEDFFKLER EMGINCTGKIVIARYGKIFRGNKVKNAMLAGAIGIILYSDPADYFAPEVQPYPKGWNLPG TAAQRGNVLNLNGAGDPLTPGYPAKEYTFRLDVEEGVGIPRIPVHPIGYNDAEILLRYLG GIAPPDKSWKGALNVSYSIGPGFTGSDSFRKVRMHVYNINKITRIYNVVGTIRGSVEPDR YVILGGHRDSWVFGAIDPTSGVAVLQEIARSFGKLMSKGWRPRRTIIFASWDAEEFGLLG STEWAEENVKILQERSIAYINSDSSIEGNYTLRVDCTPLLYQLVYKLTKEIPSPDDGFES KSLYESWLEKDPSPENKNLPRINKLGSGSDFEAYFQRLGIASGRARYTKNKKTDKYSSYP VYHTIYETFELVEKFYDPTFKKQLSVAQLRGALVYELVDSKIIPFNIQDYAEALKNYAAS IYNLSKKHDQQLTDHGVSFDSLFSAVKNFSEAASDFHKRLIQVDLNNPIAVRMMNDQLML LERAFIDPLGLPGKLFYRHIIFAPSSHNKYAGESFPGIYDAIFDIENKANSRLAWKEVKK HISIAAFTIQAAAGTLKEVL Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: (2s)-2-{[(S)-[(3s)-3-Amino-3-Carboxypropyl](Hydroxy)phosphoryl]methyl}pentanedioic Acid | Ligand Info | |||||
| Structure Description | The high resolution structure of human glutamate carboxypeptidase III (GCPIII/NAALADase II) in complex with a transition state analog of Glu-Glu | PDB:3FED | ||||
| Method | X-ray diffraction | Resolution | 1.29 Å | Mutation | No | [2] |
| PDB Sequence |
SIRWKLVSEM
55 KAENIKSFLR65 SFTKLPHLAG75 TEQNFLLAKK85 IQTQWKKFGL95 DSAKLVHYDV 105 LLSYPNETNA115 NYISIVDEHE125 TEIFKTSPPP138 DGYENVTNIV148 PPYNAFSAQG 158 MPEGDLVYVN168 YARTEDFFKL178 EREMGINCTG188 KIVIARYGKI198 FRGNKVKNAM 208 LAGAIGIILY218 SDPADYFAPE228 VQPYPKGWNL238 PGTAAQRGNV248 LNLNGAGDPL 258 TPGYPAKEYT268 FRLDVEEGVG278 IPRIPVHPIG288 YNDAEILLRY298 LGGIAPPDKS 308 WKGALNVSYS318 IGPGFTGSSF329 RKVRMHVYNI339 NKITRIYNVV349 GTIRGSVEPD 359 RYVILGGHRD369 SWVFGAIDPT379 SGVAVLQEIA389 RSFGKLMSKG399 WRPRRTIIFA 409 SWDAEEFGLL419 GSTEWAEENV429 KILQERSIAY439 INSDSSIEGN449 YTLRVDCTPL 459 LYQLVYKLTK469 EIPSPDDGFE479 SKSLYESWLE489 KDPSPENKNL499 PRINKLGSGS 509 DFEAYFQRLG519 IASGRARYTK529 NKKTDKYSSY539 PVYHTIYETF549 ELVEKFYDPT 559 FKKQLSVAQL569 RGALVYELVD579 SKIIPFNIQD589 YAEALKNYAA599 SIYNLSKKHD 609 QQLTDHGVSF619 DSLFSAVKNF629 SEAASDFHKR639 LIQVDLNNPI649 AVRMMNDQLM 659 LLERAFIDPL669 GLPGKLFYRH679 IIFAPSSHNK689 YAGESFPGIY699 DAIFDIENKA 709 NSRLAWKEVK719 KHISIAAFTI729 QAAAGTLKEV739
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PHE199
4.155
ARG200
2.758
GLY246
4.748
ASN247
2.866
HIS367
3.264
TRP371
4.992
ASP377
3.000
GLU414
2.737
GLU415
3.284
PHE416
4.725
GLY417
3.314
LEU418
4.037
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| Ligand Name: 3[N-Morpholino]propane sulfonic acid | Ligand Info | |||||
| Structure Description | Crystal structure of human Glutamate Carboxypeptidase III (GCPIII/NAALADase II), pseudo-unliganded | PDB:3FEC | ||||
| Method | X-ray diffraction | Resolution | 1.49 Å | Mutation | No | [2] |
| PDB Sequence |
SIRWKLVSEM
55 KAENIKSFLR65 SFTKLPHLAG75 TEQNFLLAKK85 IQTQWKKFGL95 DSAKLVHYDV 105 LLSYPNETNA115 NYISIVDEHE125 TEIFKTSPPD139 GYENVTNIVP149 PYNAFSAQGM 159 PEGDLVYVNY169 ARTEDFFKLE179 REMGINCTGK189 IVIARYGKIF199 RGNKVKNAML 209 AGAIGIILYS219 DPADYFAPEV229 QPYPKGWNLP239 GTAAQRGNVL249 NLNGAGDPLT 259 PGYPAKEYTF269 RLDVEEGVGI279 PRIPVHPIGY289 NDAEILLRYL299 GGIAPPDKSW 309 KGALNVSYSI319 GPGFTGSSFR330 KVRMHVYNIN340 KITRIYNVVG350 TIRGSVEPDR 360 YVILGGHRDS370 WVFGAIDPTS380 GVAVLQEIAR390 SFGKLMSKGW400 RPRRTIIFAS 410 WDAEEFGLLG420 STEWAEENVK430 ILQERSIAYI440 NSDSSIEGNY450 TLRVDCTPLL 460 YQLVYKLTKE470 IPSPDDGFES480 KSLYESWLEK490 DPSPENKNLP500 RINKLGSGSD 510 FEAYFQRLGI520 ASGRARYTKN530 KKTDKYSSYP540 VYHTIYETFE550 LVEKFYDPTF 560 KKQLSVAQLR570 GALVYELVDS580 KIIPFNIQDY590 AEALKNYAAS600 IYNLSKKHDQ 610 QLTDHGVSFD620 SLFSAVKNFS630 EAASDFHKRL640 IQVDLNNPIA650 VRMMNDQLML 660 LERAFIDPLG670 LPGKLFYRHI680 IFAPSSHNKY690 AGESFPGIYD700 AIFDIENKAN 710 SRLAWKEVKK720 HISIAAFTIQ730 AAAGTLKEV
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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 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).
Human Similarity Proteins
Human Tissue Distribution
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| Protein Name | Pfam ID | Percentage of Identity (%) | E value |
|---|---|---|---|
| #N/A | 60.000 (21/35) | 3.31E-06 | |
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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.
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| Chemical Structure based Activity Landscape of Target | Top |
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| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| References | Top | |||||
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| REF 1 | Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. | |||||
| REF 2 | Structural insight into the evolutionary and pharmacologic homology of glutamate carboxypeptidases II and III. FEBS J. 2009 Aug;276(16):4448-62. | |||||
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