Idioma:

Structure of Secreted Aspartic Proteinases from Candida: Implications for the Design of Antifungal Agents

Abad-Zapatero, Cele ; Goldman, Robert ; Muchmore, Steven W. ; Hutchins, Charles ; Oie, Tetsuro ; Stewart, Kent ; Cutfield, Sue M. ; Cutfield, John F. ; Foundling, Stephen I. ; Ray, Thomas L.

Advances in experimental medicine and biology, 1998, Vol.436, p.297-313 [Periódico revisado por pares]

Boston, MA: Springer US

Sem texto completo

Citações Citado por

Enviar para

Título:
Structure of Secreted Aspartic Proteinases from Candida: Implications for the Design of Antifungal Agents
Autor: Abad-Zapatero, Cele ; Goldman, Robert ; Muchmore, Steven W. ; Hutchins, Charles ; Oie, Tetsuro ; Stewart, Kent ; Cutfield, Sue M. ; Cutfield, John F. ; Foundling, Stephen I. ; Ray, Thomas L.
Assuntos: Antifungal Agents - pharmacology ; Aspartic Acid Endopeptidases - antagonists & inhibitors ; Aspartic Acid Endopeptidases - chemistry ; Aspartic Proteinase ; Candida - drug effects ; Candida - enzymology ; Drug Design ; Fungal Proteins ; Humans ; Models, Molecular ; Piperazine Ring ; Porcine Pepsin ; Protease Inhibitors - chemistry ; Structural Superposition ; Substrate Specificity ; Water Chain
É parte de: Advances in experimental medicine and biology, 1998, Vol.436, p.297-313
Notas: ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-3
content type line 23
ObjectType-Review-1
Descrição: Pathogens of the genus Candida can cause life threatening infections in immunocompromised patients. The three–dimensional structures of two closely related secreted aspartic proteinases from C. albicans complexed with a potent (Ki=0.17 nM) inhibitor, and an analogous enzyme from C. tropicalis reveal variations on the classical aspartic proteinase theme that dramatically alter the specificity of this class of enzymes. The novel fungal proteases present: i) an 8 residue insertion near the first disulfide (Cys45–Cys50, pepsin numbering) that results in a broad flap extending towards the active site; ii) a seven residue deletion replacing helix hN2 (Serll0–Tyrll4), which enlarges the S3 pocket; iii) a short polar connection between the two rigid body domains that alters their relative orientation and provides certain specificity; and iv) an ordered 12 residue addition at the car–boxy terminus. The same inhibitor (A–70450) binds in an extended conformation in the two variants of C albicans protease, and presents a branched structure at the P3 position. However, the conformation of the terminal methylpiperazine ring is different in the two crystals structures. The implications of these findings for the design of potent antifungal agents are discussed.
Editor: Boston, MA: Springer US
Idioma: Inglês

Links

View this record in MEDLINE/PubMed

Voltar para lista de resultados

Realização: Logos de Redes Sociais:

Structure of Secreted Aspartic Proteinases from Candida: Implications for the Design of Antifungal Agents

Abad-Zapatero, Cele ; Goldman, Robert ; Muchmore, Steven W. ; Hutchins, Charles ; Oie, Tetsuro ; Stewart, Kent ; Cutfield, Sue M. ; Cutfield, John F. ; Foundling, Stephen I. ; Ray, Thomas L.

Boston, MA: Springer US

Buscando em bases de dados remotas. Favor aguardar.