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PDBsum entry 1zap
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Aspartic protease
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PDB id
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1zap
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References listed in PDB file
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Key reference
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Title
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Structure of a secreted aspartic protease from c. Albicans complexed with a potent inhibitor: implications for the design of antifungal agents.
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Authors
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C.Abad-Zapatero,
R.Goldman,
S.W.Muchmore,
C.Hutchins,
K.Stewart,
J.Navaza,
C.D.Payne,
T.L.Ray.
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Ref.
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Protein Sci, 1996,
5,
640-652.
[DOI no: ]
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PubMed id
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Abstract
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The three-dimensional structure of a secreted aspartic protease from Candida
albicans complexed with a potent inhibitor reveals variations on the classical
aspartic protease theme that dramatically alter the specificity of this class of
enzymes. The structure presents: (1) an 8-residue insertion near the first
disulfide (Cys 45-Cys 50, pepsin numbering) that results in a broad flap
extending toward the active site; (2) a 7-residue deletion replacing helix hN2
(Ser 110-Tyr 114), which enlarges the S3 pocket; (3) a short polar connection
between the two rigid body domains that alters their relative orientation and
provides certain specificity; and (4) an ordered 11-residue addition at the
carboxy terminus. The inhibitor binds in an extended conformation and presents a
branched structure at the P3 position. The implications of these findings for
the design of potent antifungal agents are discussed.
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Figure 1.
Fig. 1. Stereodiagram of lectrondensity map corresponding to theinsetionat the first disulfide bond(Cys47-Cys 59)
of the SAP2X tructure. The figurecomprissresidues Ile 45-Lys 60 withthecorrespondingelectrondensity (2F, - ,; =
1 level). It illustratesthequality of the electron densityandtherigidity of the conformation. Residues are labeledsequentially
from Ile 45 to Lys 60. See Fiure for therelative disposition of this loop inrelation to the est of the structure.
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Figure 7.
Fig. 7. Schematic representation of the hydrogen bondinginteractions of he -7045 inhibitor with theproteinatoms the
SAPZX and of thedifferent enzyme pockets corresponding to theinhibitor subsites.
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The above figures are
reprinted
from an Open Access publication published by the Protein Society:
Protein Sci
(1996,
5,
640-652)
copyright 1996.
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Secondary reference #1
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Title
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The crystal structure of a major secreted aspartic proteinase from candida albicans in complexes with two inhibitors.
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Authors
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S.M.Cutfield,
E.J.Dodson,
B.F.Anderson,
P.C.Moody,
C.J.Marshall,
P.A.Sullivan,
J.F.Cutfield.
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Ref.
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Structure, 1995,
3,
1261-1271.
[DOI no: ]
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PubMed id
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Figure 5.
Figure 5. Hydrogen-bonding diagrams. (a) A70450 bound to SAP2.
(b) Pepstatin bound to SAP2. Distances of less than 3.5
å, between electronegative atoms, are indicated. Figure
5. Hydrogen-bonding diagrams. (a) A70450 bound to SAP2. (b)
Pepstatin bound to SAP2. Distances of less than 3.5 å,
between electronegative atoms, are indicated.
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Figure 8.
Figure 8. Molecular surface of SAP2, with bound inhibitor
A70450. The diagram is coloured to reflect electrostatic
potential: negative charges in red, positive charges in blue.
The inhibitor is oriented with P4 on the right and P′2 on the
left. Figure 8. Molecular surface of SAP2, with bound
inhibitor A70450. The diagram is coloured to reflect
electrostatic potential: negative charges in red, positive
charges in blue. The inhibitor is oriented with P4 on the right
and P′2 on the left. (Figure generated by MOLVIEWER [MJ
Hartshorn, University of York].)
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The above figures are
reproduced from the cited reference
with permission from Cell Press
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