ISDA: 3N3G

Deposition Date 2010-05-20

Release Date 2010-07-14

Last Version Date 2024-12-25

Entry Detail

PDB ID:

3N3G

Keywords:

HYDROLASE

Title:

4-(3-Trifluoromethylphenyl)-pyrimidine-2-carbonitrile as cathepsin S inhibitors: N3, not N1 is critically important

Biological Source:

Source Organism(s):

Homo sapiens (Taxon ID: 9606)

Expression System(s):

Trichoplusia ni

Method Details:

Experimental Method:

X-RAY DIFFRACTION

Resolution:

1.60 Å

R-Value Free:

0.26

R-Value Work:

0.22

R-Value Observed:

0.22

Space Group:

P 41 2 2

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Macromolecular Entities

Structures with similar UniProt ID

Protein Blast

Polymer Type:polypeptide(L)
Molecule:Cathepsin S
Gene (Uniprot):CTSS
Chain IDs:A, B
Chain Length:217
Number of Molecules:2
Biological Source:Homo sapiens

UniProt ID:P25774 Pfam ID:PF00112 EC:3.4.22.27

Ligand Molecules

935

93N

DMS

GOL

PEG

SO4

Primary Citation

4-(3-Trifluoromethylphenyl)-pyrimidine-2-carbonitrile as cathepsin S inhibitors: N3, not N1 is critically important.

Cai, J, Fradera, X, van Zeeland, M, Dempster, M, Cameron, K.S, Bennett, D.J, Robinson, J, Popplestone, L, Baugh, M, Westwood, P, Bruin, J, Hamilton, W, Kinghorn, E, Long, C, Uitdehaag, J.C.Show

Bioorg. Med. Chem. Lett. 20 4507 4510 (2010)

PMID: 20580231 DOI: 10.1016/j.bmcl.2010.06.043

Abstact

Using computer aided modelling studies, a new extended P2/S2 interaction was identified. This extended region can accommodate a variety of functional groups, such as aryls and basic amines. It was discovered that the N3 nitrogen of the pyrimidine-2-carbonitrile is critical for its cathepsin cysteine protease inhibition. N1 nitrogen also contributes to the inhibitory activity, but to a very limited degree. An 'in situ double activation' mechanism was proposed to explain these results.

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Protein

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Disease

Primary Citation of related structures

Abstact

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