Target Information
| Target General Information | Top | |||||
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| Target ID |
T92460
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| Target Name |
Guanine deaminase (GDA)
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| Synonyms |
p51-nedasin; KIAA1258; Guanine aminohydrolase; Guanase; GAH
Click to Show/Hide
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| Gene Name |
GDA
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Catalyzes the hydrolytic deamination of guanine, producing xanthine and ammonia.
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| BioChemical Class |
Metallo-dependent hydrolase superfamily. ATZ/TRZ family
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| UniProt ID | ||||||
| EC Number |
EC 3.5.4.3
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| Sequence |
MCAAQMPPLAHIFRGTFVHSTWTCPMEVLRDHLLGVSDSGKIVFLEEASQQEKLAKEWCF
KPCEIRELSHHEFFMPGLVDTHIHASQYSFAGSSIDLPLLEWLTKYTFPAEHRFQNIDFA EEVYTRVVRRTLKNGTTTACYFATIHTDSSLLLADITDKFGQRAFVGKVCMDLNDTFPEY KETTEESIKETERFVSEMLQKNYSRVKPIVTPRFSLSCSETLMGELGNIAKTRDLHIQSH ISENRDEVEAVKNLYPSYKNYTSVYDKNNLLTNKTVMAHGCYLSAEELNVFHERGASIAH CPNSNLSLSSGFLNVLEVLKHEVKIGLGTDVAGGYSYSMLDAIRRAVMVSNILLINKVNE KSLTLKEVFRLATLGGSQALGLDGEIGNFEVGKEFDAILINPKASDSPIDLFYGDFFGDI SEAVIQKFLYLGDDRNIEEVYVGGKQVVPFSSSV 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: Valaciclovir | Ligand Info | |||||
| Structure Description | HUMAN GUANINE DEAMINASE IN COMPLEX WITH VALACYCLOVIR | PDB:4AQL | ||||
| Method | X-ray diffraction | Resolution | 1.99 Å | Mutation | No | [2] |
| PDB Sequence |
LAHIFRGTFV
18 HSTWTCPMEV28 LRDHLLGVSD38 SGKIVFLEEA48 SQQEKLAKEW58 CFKPCEIREL 68 SHHEFFMPGL78 VDTHIHASQY88 SFAGSSIDLP98 LLEWLTKYTF108 PAEHRFQNID 118 FAEEVYTRVV128 RRTLKNGTTT138 ACYFATIHTD148 SSLLLADITD158 KFGQRAFVGK 168 VCMDLNDTFP178 EYKETTEESI188 KETERFVSEM198 LQKNYSRVKP208 IVTPRFSLSC 218 SETLMGELGN228 IAKTRDLHIQ238 SHISENRDEV248 EAVKNLYPSY258 KNYTSVYDKN 268 NLLTNKTVMA278 HGCYLSAEEL288 NVFHERGASI298 AHCPNSNLSL308 SSGFLNVLEV 318 LKHEVKIGLG328 TDVAGGYSYS338 MLDAIRRAVM348 VSNILLINKV358 NEKSLTLKEV 368 FRLATLGGSQ378 ALGLDGEIGN388 FEVGKEFDAI398 LINPKASDSP408 IDLFYGDFFG 418 DISEAVIQKF428 LYLGDDRNIE438 EVYVGGKQVV448 PF
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HIS84
3.424
GLN87
2.948
LEU99
3.088
LEU100
2.849
TRP102
3.827
LEU103
3.503
THR107
4.008
GLU111
4.645
ARG213
2.848
PHE214
3.059
LEU216
3.595
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| Ligand Name: Xanthine | Ligand Info | |||||
| Structure Description | Human guanine deaminase (guaD) in complex with zinc and its product Xanthine. | PDB:2UZ9 | ||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [3] |
| PDB Sequence |
PLAHIFRGTF
17 VHSTWTCPME27 VLRDHLLGVS37 DSGKIVFLEE47 ASQQEKLAKE57 WCFKPCEIRE 67 LSHHEFFMPG77 LVDTHIHASQ87 YSFAGSSIDL97 PLLEWLTKYT107 FPAEHRFQNI 117 DFAEEVYTRV127 VRRTLKNGTT137 TACYFATIHT147 DSSLLLADIT157 DKFGQRAFVG 167 KVCMDLNDTF177 PEYKETTEES187 IKETERFVSE197 MLQKNYSRVK207 PIVTPRFSLS 217 CSETLMGELG227 NIAKTRDLHI237 QSHISENRDE247 VEAVKNLYPS257 YKNYTSVYDK 267 NNLLTNKTVM277 AHGCYLSAEE287 LNVFHERGAS297 IAHCPNSNLS307 LSSGFLNVLE 317 VLKHEVKIGL327 GTDVAGGYSY337 SMLDAIRRAV347 MVSNILLINK357 VNEKSLTLKE 367 VFRLATLGGS377 QALGLDGEIG387 NFEVGKEFDA397 ILINPKASDS407 PIDLFYGDFF 417 GDISEAVIQK427 FLYLGDDRNI437 EEVYVGGKQV447 VPFS
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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 Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
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
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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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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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Purine metabolism | hsa00230 | Affiliated Target |
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| Class: Metabolism => Nucleotide metabolism | Pathway Hierarchy | ||
| Degree | 4 | Degree centrality | 4.30E-04 | Betweenness centrality | 6.08E-04 |
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| Closeness centrality | 1.62E-01 | Radiality | 1.24E+01 | Clustering coefficient | 1.67E-01 |
| Neighborhood connectivity | 1.13E+01 | Topological coefficient | 2.76E-01 | Eccentricity | 13 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| 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 | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
| 1 | Purine metabolism | |||||
| 2 | Metabolic pathways | |||||
| References | Top | |||||
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| REF 1 | Studies on guanine deaminase and its inhibitors in rat tissue. Biochem J. 1967 Mar;102(3):691-704. | |||||
| REF 2 | Pan-pathway based interaction profiling of FDA-approved nucleoside and nucleobase analogs with enzymes of the human nucleotide metabolism. PLoS One. 2012;7(5):e37724. | |||||
| REF 3 | Human Guanine Deaminase (Guad) in Complex with Zinc and its Product Xhantine | |||||
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