1LYW

CATHEPSIN D AT PH 7.5

Summary for 1LYW

• Entry DOI: 10.2210/pdb1lyw/pdb
• Descriptor: CATHEPSIN D, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, ... (4 entities in total)
• Functional Keywords: aspartic protease, hydrolase, glycoprotein
• Biological source: Homo sapiens (human); More
• Cellular location: Lysosome: P07339 P07339
• Total number of polymer chains: 8
• Total formula weight: 148789.81

Authors

Lee, A.Y.,Gulnik, S.V.,Erickson, J.W. (deposition date: 1998-06-30, release date: 1999-07-22, Last modification date: 2024-11-06)

Primary citation

Lee, A.Y.,Gulnik, S.V.,Erickson, J.W.
Conformational switching in an aspartic proteinase.
Nat.Struct.Biol., 5:866-871, 1998

PubMed Abstract: The crystal structure of a catalytically inactive form of cathepsin D (CatDhi) has been obtained at pH 7.5. The N-terminal strand relocates by 30 A from its position in the interdomain beta-sheet and inserts into the active site cleft, effectively blocking substrate access. CatDhi has a five-stranded interdomain beta-sheet and resembles Intermediate 3, a hypothetical structure proposed to be transiently formed during proteolytic activation of the proenzyme precursor. Interconversion between active and inactive forms of CatD is reversible and may be regulated by an ionizable switch involving the carboxylate side chains of Glu 5, Glu 180, and Asp 187. Our findings provide a structural basis for the pH-dependent regulation of aspartic proteinase activity and suggest a novel mechanism for pH-dependent modulation of substrate specificity.

PubMed: 9783744
DOI: 10.1038/2306

Experimental method

X-RAY DIFFRACTION (2.5 Å)