Nalazite se na CroRIS probnoj okolini. Ovdje evidentirani podaci neće biti pohranjeni u Informacijskom sustavu znanosti RH. Ako je ovo greška, CroRIS produkcijskoj okolini moguće je pristupi putem poveznice www.croris.hr
izvor podataka: crosbi

The large scale conformational change of the human DPP III – substrate prefers the "closed" form (CROSBI ID 184577)

Prilog u časopisu | izvorni znanstveni rad | međunarodna recenzija

Tomić, Antonija ; Gonzalez, Miguel ; Tomić, Sanja The large scale conformational change of the human DPP III – substrate prefers the "closed" form // Journal of chemical information and modeling, 52 (2012), 6; 1583-1594. doi: 10.1021/ci300141k

Podaci o odgovornosti

Tomić, Antonija ; Gonzalez, Miguel ; Tomić, Sanja

engleski

The large scale conformational change of the human DPP III – substrate prefers the "closed" form

Human dipeptidyl peptidase III (DPP III) is a two domain metallo–peptidase from M49 family. The wide inter–domain cleft and broad substrate specificity suggest that this enzyme could experience significant conformational change. Long (> 100 ns) molecular dynamics (MD) simulations of DPP III revealed large range conformational changes of the protein suggesting the pre-existing equilibrium model for a substrate binding. The binding free energy calculations revealed tighter binding of the preferred synthetic substrate Arg–Arg–2–naphtylamide to the "closed" than to the "open" DPP III conformation. Our assumption that Asp372 plays a crucial role in the large scale inter–domain closure was approved by the MD simulations of the Asp372Ala variant. During the same simulation time the variant remained more "open" than the wild type protein. Apparently, Ala was not as efficient as Asp in establishing the inter–domain interactions. According to the MM–PBSA calculations, the electrostatic component of the free energy of solvation turned out to be higher for the "closed" protein than for its less compact form. However, gain in entropy due to water release from the inter–domain cleft nicely balanced this negative effect.

metallo-peptidase; human dipeptidyl peptidase III; large scale conformational changes; molecular dynamic simulations; substrate binding; binding free energy

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

Podaci o izdanju

52 (6)

2012.

1583-1594

objavljeno

1549-9596

10.1021/ci300141k

Povezanost rada

Kemija

Poveznice
Indeksiranost