Importance of loop dynamics in the neocarzinostatin chromophore binding and release mechanisms.
Phys Chem Chem Phys
; 12(14): 3443-9, 2010 Apr 14.
Article
en En
| MEDLINE
| ID: mdl-20336247
ABSTRACT
Neocarzinostatin (NCS) is an antitumor chromophore carrier protein with many therapeutic applications. To characterize its binding and release mechanism, we have carried out molecular dynamics (MD) simulations for apo-NCS and holo-NCS. Although the beta-sheet regions of the protein exhibit restricted motion, large atomic fluctuations were observed in the loop regions, especially loop 99-104. This loop undergoes a "door-opening" motion that can facilitate chromophore binding and release. Calculated NMR order parameters confirm the simulated loop flexibility. We also provide a proposed explanation for the release rate difference for two mutants F78L and F78A through our simulation. The binding site structures of holo-NCS were also validated by chemical shift perturbations. Based on these results, a new binding and release mechanism for the NCS chromophore is proposed.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Antineoplásicos
Idioma:
En
Revista:
Phys Chem Chem Phys
Asunto de la revista:
BIOFISICA
/
QUIMICA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos