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Comparative modelling of barley‐grain aspartic proteinase: A structural rationale for observed hydrolytic specificity
Author(s) -
Guruprasad Kunchur,
Törmäkangas Kirsi,
Kervinen Jukka,
Blundell Tom L.
Publication year - 1994
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(94)00935-x
Subject(s) - hydrolysis , chemistry , biochemistry
A model of the barley‐grain aspartic proteinase (HvAP; Hordeum vulgare aspartic proteinase) has been constructed using the rule‐based comparative modelling approach encoded in the COMPOSER suite of computer programs. The model was based on the high resolution crystal structures of six highly homologous aspartic proteinases. Results suggest that the overall three‐dimensional structure of HvAP (excluding the plant‐specific insert; 104 residues in HvAP) is closer to human cathepsin D than other aspartic proteinases of known three‐dimensional structure. Comparisons of the complexes with the substrate modelled in the active site of HvAP with those of the same substrate modelled in the active site of other aspartic proteinases of known three‐dimensional structure and specificity, define residues that may influence hydrolytic specificity of the barley enzyme. We have identified residues in the S 4 (Ala 12 ), S 3 (Gln 13 , Thr 111 ), S 2 (Ala 222 , Thr 287 , Met 289 ), S ′ 1 and S ′ 3 (Ile 291 ), S ′ 2 and S ′ 3 (Gln 74 ), S ′ 2 (Arg 295 ), and S ′ 3 (Pro 292 ) pockets, that may account for the observed trends in the kinetic behaviour and specificity when compared to other aspartic proteinases. The plant‐specific inserted sequence, which may play a role in the transport of HvAP to plant vacuoles (lysosomes), is similar to the saposins and is predicted to be a mixed α‐helical and β‐strand domain.