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PDBsum entry 1epp
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Hydrolase/hydrolase inhibitor
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PDB id
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1epp
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Analyses of ligand binding in five endothiapepsin crystal complexes and their use in the design and evaluation of novel renin inhibitors.
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Authors
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E.A.Lunney,
H.W.Hamilton,
J.C.Hodges,
J.S.Kaltenbronn,
J.T.Repine,
M.Badasso,
J.B.Cooper,
C.Dealwis,
B.A.Wallace,
W.T.Lowther.
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Ref.
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J Med Chem, 1993,
36,
3809-3820.
[DOI no: ]
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PubMed id
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Abstract
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Five renin inhibitors were cocrystallized with endothiapepsin, a fungal enzyme
homologous to renin. Crystal structures of inhibitor-bound complexes have
provided invaluable insight regarding the three-dimensional structure of the
aspartic proteinase family of enzymes, as well as the steric and polar
interactions that occur between the proteins and the bound ligands. Beyond this,
subtleties of binding have been revealed, including multiple subsite binding
modes and subsite interdependencies. This information has been applied in the
design of novel potent renin inhibitors and in the understanding of
structure-activity relationships and enzyme selectivities.
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Secondary reference #1
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Title
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A structural comparison of 21 inhibitor complexes of the aspartic proteinase from endothia parasitica.
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Authors
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D.Bailey,
J.B.Cooper.
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Ref.
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Protein Sci, 1994,
3,
2129-2143.
[DOI no: ]
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
perfect match.
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Figure 3.
Fig. 3. hydrogen bondinteractions with inhibitorsare shown (top) with agraph showing te donor-acceptor dis-
tances for the 21 nhibitor complexes (+ indicates an 0. . .H-N interaction, @ indicates an 0. . .H-N nteraction with an
at theproton greater than 160'. and X indicates n 0. . .H-0 interaction). Some of theiteractions with the aspartate carbox-
yls willbe van er Waals contactsratherthan hydrogen bonds (see text for discussion of proton locations).
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Figure 5.
Fig. 5. A: distribution of x, angles observed for each position of the inhibitors. The distribution of x2 angles.
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The above figures are
reproduced from the cited reference
with permission from the Protein Society
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Secondary reference #2
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Title
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X-Ray analyses of aspartic proteinases. The three-Dimensional structure at 2.1 a resolution of endothiapepsin.
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Authors
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T.L.Blundell,
J.A.Jenkins,
B.T.Sewell,
L.H.Pearl,
J.B.Cooper,
I.J.Tickle,
B.Veerapandian,
S.P.Wood.
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Ref.
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J Mol Biol, 1990,
211,
919-941.
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PubMed id
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