cathepsin D

Target not currently curated in GtoImmuPdb

Target id: 2345

Nomenclature: cathepsin D

Gene and Protein Information
Species	TM	AA	Chromosomal Location	Gene Symbol	Gene Name	Reference
Human	-	412	11p15.5	CTSD	cathepsin D
Mouse	-	410	7 F5	Ctsd	cathepsin D
Rat	-	407	1q41	Ctsd	cathepsin D

Previous and Unofficial Names
CatD \| CD \| ceroid-lipofuscinosis, neuronal 10 \| CLN10 \| CPSD

Database Links
Specialist databases
MEROPS	A01.009 (Hs)
Other databases
Alphafold	P07339 (Hs), P18242 (Mm), P24268 (Rn)
BRENDA	3.4.23.5
CATH/Gene3D	2.40.70.10
ChEMBL Target	CHEMBL2581 (Hs)
Ensembl Gene	ENSG00000117984 (Hs), ENSMUSG00000007891 (Mm), ENSRNOG00000020206 (Rn)
Entrez Gene	1509 (Hs), 13033 (Mm), 171293 (Rn)
Human Protein Atlas	ENSG00000117984 (Hs)
KEGG Enzyme	3.4.23.5
KEGG Gene	hsa:1509 (Hs), mmu:13033 (Mm), rno:171293 (Rn)
OMIM	116840 (Hs)
Orphanet	ORPHA159489 (Hs)
Pharos	P07339 (Hs)
RefSeq Nucleotide	NM_001909 (Hs), NM_009983 (Mm), NM_134334 (Rn)
RefSeq Protein	NP_001900 (Hs), NP_034113 (Mm), NP_599161 (Rn)
UniProtKB	P07339 (Hs), P18242 (Mm), P24268 (Rn)
Wikipedia	CTSD (Hs)

Selected 3D Structures

Image of receptor 3D structure from RCSB PDB

Description:	Crystal structure of human cathepsin D in complex with macrocyclic inhibitor 33
PDB Id:	6QBH
Ligand:	compound 33 [PMID: 32003991]
Resolution:	1.85Å
Species:	Human
References:	3

Enzyme Reaction

EC Number: 3.4.23.5

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Inhibitors

Key to terms and symbols

View all chemical structures

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Ligand		Sp.	Action	Value	Parameter	Reference
compound 3 [PMID: 8410973]		Hs	Inhibition	7.7	pK_i	5
⤷	pK_i 7.7 (K_i 1.8x10^-8 M) [5]
β-secretase inhibitor IV		Hs	Inhibition	6.3	pK_i	2
⤷	pK_i 6.3 (K_i 4.48x10^-7 M) [2]
compound 1 [PMID: 10498202]		Hs	Inhibition	9.2	pIC₅₀	1
⤷	pIC₅₀ 9.2 (IC₅₀ 7x10^-10 M) [1]
compound 33 [PMID: 32003991]		Hs	Inhibition	8.6	pIC₅₀	3
⤷	pIC₅₀ 8.6 (IC₅₀ 2.5x10^-9 M) [3]
grassystatin A		Hs	Inhibition	7.6	pIC₅₀	4
⤷	pIC₅₀ 7.6 (IC₅₀ 2.65x10^-8 M) [4]

Immuno Process Associations

Immuno Process:

Inflammation

Immuno Process:

Antigen presentation

Immuno Process:

Cellular signalling

Clinically-Relevant Mutations and Pathophysiology

Disease:

Ceroid lipofuscinosis, neuronal, 10

Synonyms:	Cathepsin D deficiency CLN10 disease [Orphanet: ORPHA228337] Neuronal ceroid lipofuscinosis [Disease Ontology: DOID:14503]
Disease Ontology:	DOID:14503
OMIM:	610127
Orphanet:	ORPHA228337

References

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1. Dumas J, Brittelli D, Chen J, Dixon B, Hatoum-Mokdad H, König G, Sibley R, Witowsky J, Wong S. (1999) Synthesis and structure activity relationships of novel small molecule cathepsin D inhibitors. Bioorg Med Chem Lett, 9 (17): 2531-6. [PMID:10498202]

2. Ghosh AK, Kumaragurubaran N, Hong L, Kulkarni SS, Xu X, Chang W, Weerasena V, Turner R, Koelsch G, Bilcer G et al.. (2007) Design, synthesis, and X-ray structure of potent memapsin 2 (beta-secretase) inhibitors with isophthalamide derivatives as the P2-P3-ligands. J Med Chem, 50 (10): 2399-407. [PMID:17432843]

3. Houštecká R, Hadzima M, Fanfrlík J, Brynda J, Pallová L, Hánová I, Mertlíková-Kaiserová H, Lepšík M, Horn M, Smrčina M et al.. (2020) Biomimetic Macrocyclic Inhibitors of Human Cathepsin D: Structure-Activity Relationship and Binding Mode Analysis. J Med Chem, 63 (4): 1576-1596. [PMID:32003991]

4. Kwan JC, Eksioglu EA, Liu C, Paul VJ, Luesch H. (2009) Grassystatins A-C from marine cyanobacteria, potent cathepsin E inhibitors that reduce antigen presentation. J Med Chem, 52 (18): 5732-47. [PMID:19715320]

5. Rao CM, Scarborough PE, Kay J, Batley B, Rapundalo S, Klutchko S, Taylor MD, Lunney EA, Humblet CC, Dunn BM. (1993) Specificity in the binding of inhibitors to the active site of human/primate aspartic proteinases: analysis of P2-P1-P1'-P2' variation. J Med Chem, 36 (18): 2614-20. [PMID:8410973]