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Is histoaspartic protease a serine protease with a pepsin‐like fold?
Author(s) -
Andreeva N.,
Bogdanovich P.,
Kashparov I.,
Popov M.,
Stengach M.
Publication year - 2004
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.20078
Subject(s) - protease , serine protease , chemistry , proteases , enzyme , tmprss6 , biochemistry , masp1 , oxyanion hole , homology modeling , serine , stereochemistry
Abstract The primary structure of the so‐called histoaspartic protease from Plasmodium falciparum has a very high percentage of identity and homology with the pepsin‐like enzyme plasmepsin II. A homology modeling approach was used to calculate the three‐dimensional structure of the enzyme. Molecular dynamics (MD) simulations were applied to find those structural properties of the histoaspartic protease that had a tendency to remain stable during all runs. The results have shown that hydrogen‐bonded residues Ser37–His34–Asp214 are arranged without any strain, in a manner that resembles the active site of a serine protease, while Ser38 and Asn39 take up positions appropriate to formation of an oxyanion hole. Although there are several important differences between the enzyme and plasmepsin II, all of the structural features associated with a typical pepsin‐like aspartic protease are present in the final model of the histoaspartic protease. A possibility that this enzyme may function as a serine protease is discussed. Proteins 2004. © 2004 Wiley‐Liss, Inc.