PDBsum entry: 1eag

Hydrolase/hydrolase inhibitor

PDB id: 1eag

Contents

Protein chain

339 a.a. *

Ligands

A70

Waters ×119

* Residue conservation analysis

PDB id:

1eag

Name:

Hydrolase/hydrolase inhibitor

Title:

Secreted aspartic proteinase (sap2) from candida albicans co with a70450

Structure:

Aspartic proteinase (sap2 gene product). Chain: a. Synonym: sap2, candidapepsin. Ec: 3.4.23.24

Source:

Candida albicans. Organism_taxid: 5476. Atcc: 10261

Biol. unit:

Dimer (from PQS)

Resolution:

2.10Å R-factor: 0.195 R-free: 0.268

Authors:

J.F.Cutfield,S.M.Cutfield

Key ref:

S.M.Cutfield et al. (1995). The crystal structure of a major secreted aspartic proteinase from Candida albicans in complexes with two inhibitors. Structure, 3, 1261-1271. PubMed id: 8591036 DOI: 10.1016/S0969-2126(01)00261-1

Date:

31-May-96 Release date: 23-Dec-96

Protein chain

Q8NKF1  (Q8NKF1_CANAL) -  Candidapepsin-2

Seq: 398 a.a.

Struc: 339 a.a.

 Gene Ontology (GO) functional annotation 

• Cellular component: extracellular region (1 term)
• Biological process: proteolysis (1 term)
• Biochemical function: hydrolase activity (3 terms)

DOI no: 10.1016/S0969-2126(01)00261-1

Structure 3:1261-1271 (1995)

PubMed id: 8591036

The crystal structure of a major secreted aspartic proteinase from Candida albicans in complexes with two inhibitors.

S.M.Cutfield, E.J.Dodson, B.F.Anderson, P.C.Moody, C.J.Marshall, P.A.Sullivan, J.F.Cutfield.

ABSTRACT

BACKGROUND: Infections caused by Candida albicans, a common fungal pathogen of humans, are increasing in incidence, necessitating development of new therapeutic drugs. Secreted aspartic proteinase (SAP) activity is considered an important virulence factor in these infections and might offer a suitable target for drug design. Amongst the various SAP isozymes, the SAP2 gene product is the major form expressed in a number of C. albicans strains. RESULTS: The three-dimensional structures of SAP2 complexed with the tight-binding inhibitor A70450 (a synthetic hexapeptide analogue) and with the general aspartic proteinase inhibitor pepstatin A (a microbial natural product) have been determined to 2.1 A and 3.0 A resolution, respectively. Although the protein structure retains the main features of a typical aspartic proteinase, it also shows some significant differences, due mainly to several sequence insertions and deletions (as revealed by homology modelling), that alter the shape of the binding cleft. There is also considerable variation in the C-terminal structural domain. CONCLUSIONS: The differences in side chains, and in the conformations adopted by the two inhibitors, particularly at their P4, P3 and P'2 positions (using standard notation for protease-inhibitor residues), allows the A70450 structure to complement, more accurately, that of the substrate-binding site of SAP2. Some differences in the binding clefts of other SAP isoenzymes may be deduced from the SAP2 structure.

Selected figure(s)

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.

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].)

The above figures are reprinted by permission from Cell Press: Structure (1995, 3, 1261-1271) copyright 1995.

Figures were selected by an automated process.