3iej

From Proteopedia

Pyrazole-based Cathepsin S Inhibitors with Arylalkynes as P1 Binding Elements

Structural highlights

3iej is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.18Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CATS_HUMAN Thiol protease. Key protease responsible for the removal of the invariant chain from MHC class II molecules. The bond-specificity of this proteinase is in part similar to the specificities of cathepsin L and cathepsin N.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

A crystal structure of 1 bound to a Cys25Ser mutant of cathepsin S helped to elucidate the binding mode of a previously disclosed series of pyrazole-based CatS inhibitors and facilitated the design of a new class of arylalkyne analogs. Optimization of the alkyne and tetrahydropyridine portions of the pharmacophore provided potent CatS inhibitors (IC50=40-300 nM), and an X-ray structure of 32 revealed that the arylalkyne moiety binds in the S1 pocket of the enzyme.

Pyrazole-based cathepsin S inhibitors with arylalkynes as P1 binding elements.,Ameriks MK, Axe FU, Bembenek SD, Edwards JP, Gu Y, Karlsson L, Randal M, Sun S, Thurmond RL, Zhu J Bioorg Med Chem Lett. 2009 Nov 1;19(21):6131-4. Epub 2009 Sep 10. PMID:19773165^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ameriks MK, Axe FU, Bembenek SD, Edwards JP, Gu Y, Karlsson L, Randal M, Sun S, Thurmond RL, Zhu J. Pyrazole-based cathepsin S inhibitors with arylalkynes as P1 binding elements. Bioorg Med Chem Lett. 2009 Nov 1;19(21):6131-4. Epub 2009 Sep 10. PMID:19773165 doi:10.1016/j.bmcl.2009.09.014