1NB3

Crystal structure of stefin A in complex with cathepsin H: N-terminal residues of inhibitors can adapt to the active sites of endo-and exopeptidases

Summary for 1NB3

• Entry DOI: 10.2210/pdb1nb3/pdb
• Related: 1nb5
• Descriptor: Cathepsin H, CATHEPSIN H MINI CHAIN, Stefin A, ... (5 entities in total)
• Functional Keywords: cysteine proteinase, aminopeptidase, cystatin, enzyme-inhibitor complex, hydrolase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 12
• Total formula weight: 147137.62

Authors

Jenko, S.,Dolenc, I.,Guncar, G.,Dobersek, A.,Podobnik, M.,Turk, D. (deposition date: 2002-12-02, release date: 2003-02-18, Last modification date: 2023-08-16)

Primary citation

Jenko, S.,Dolenc, I.,Guncar, G.,Dobersek, A.,Podobnik, M.,Turk, D.
Crystal structure of stefin A in complex with cathepsin H: N-terminal residues of inhibitors can adapt to the active sites of endo- and exopeptidases
J.Mol.Biol., 326:875-885, 2003

PubMed Abstract: Binding of cystatin-type inhibitors to papain-like exopeptidases cannot be explained by the stefin B-papain complex. The crystal structure of human stefin A bound to an aminopeptidase, porcine cathepsin H, has been determined in monoclinic and orthorhombic crystal forms at 2.8A and 2.4A resolutions, respectively. The asymmetric unit of each form contains four complexes. The structures are similar to the stefin B-papain complex, but with a few distinct differences. On binding, the N-terminal residues of stefin A adopt the form of a hook, which pushes away cathepsin H mini-chain residues and distorts the structure of the short four residue insertion (Lys155A-Asp155D) unique to cathepsin H. Comparison with the structure of isolated cathepsin H shows that the rims of the cathepsin H structure are slightly displaced (up to 1A) from their position in the free enzyme. Furthermore, comparison with the stefin B-papain complex showed that molecules of stefin A bind about 0.8A deeper into the active site cleft of cathepsin H than stefin B into papain. The approach of stefin A to cathepsin H induces structural changes along the interaction surface of both molecules, whereas no such changes were observed in the stefin B-papain complex. Carboxymethylation of papain seems to have prevented the formation of the genuine binding geometry between a papain-like enzyme and a cystatin-type inhibitor as we observe it in the structure presented here.

PubMed: 12581647
DOI: 10.1016/S0022-2836(02)01432-8

Experimental method

X-RAY DIFFRACTION (2.8 Å)