J 2007

Dispersive interactions govern strong thermal stability of a protein

VONDRÁŠEK, Jiří; Tomáš KUBAŘ; Francis E. JENNEY, JR.; Michael W.W. ADAMS; Milan KOŽÍŠEK et al.

Základní údaje

Originální název

Dispersive interactions govern strong thermal stability of a protein

Název česky

Disperzní interakce determinují velkou termální stabilitu proteinu

Autoři

VONDRÁŠEK, Jiří; Tomáš KUBAŘ; Francis E. JENNEY, JR.; Michael W.W. ADAMS; Milan KOŽÍŠEK; Jiří ČERNÝ; Vladimír SKLENÁŘ a Pavel HOBZA

Vydání

Chemistry- A European Journal, 2007, 0947-6539

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10610 Biophysics

Stát vydavatele

Německo

Utajení

není předmětem státního či obchodního tajemství

Odkazy

Impakt faktor

Impact factor: 5.330

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/07:00022789

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

ab initio calculations; hydrophobic core; hydrophobic effect; molecular modeling; NMR spectroscopy

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 20. 6. 2008 12:55, prof. RNDr. Vladimír Sklenář, DrSc.

Anotace

V originále

Rubredoxin from the hyperthermophile Pyrococcus furiosus (Pf Rd) is an extremely thermostable protein, which makes it an attractive subject of protein folding and stability studies. A fundamental question arises of what the reason for such extreme stability is and how it can be elucidated from a complex set of inter-atomic interactions. We addressed this issue first theoretically through a computational analysis of the hydrophobic core of the protein and its mutants including the interactions taking place inside the core. Here we show that a single mutation of one phenylalanine's residues inside the protein's hydrophobic core results in a dramatic decrease in its thermal stability. The calculated unfolding Gibbs energy as well as the stabilisation energy differences between a few core residues follow the same trend as the melting temperature of protein variants determined experimentally by microcalorimetry measurements. NMR experiments have shown that the only part of the protein affected by mutation is the reasonably rearranged hydrophobic core. It is hence concluded that stabilisation energies, which are dominated by London dispersion, represent the main source of stability of this protein.

Česky

Rubredoxin from the hyperthermophile Pyrococcus furiosus (Pf Rd) is an extremely thermostable protein, which makes it an attractive subject of protein folding and stability studies. A fundamental question arises of what the reason for such extreme stability is and how it can be elucidated from a complex set of inter-atomic interactions. We addressed this issue first theoretically through a computational analysis of the hydrophobic core of the protein and its mutants including the interactions taking place inside the core. Here we show that a single mutation of one phenylalanine's residues inside the protein's hydrophobic core results in a dramatic decrease in its thermal stability. The calculated unfolding Gibbs energy as well as the stabilisation energy differences between a few core residues follow the same trend as the melting temperature of protein variants determined experimentally by microcalorimetry measurements. NMR experiments have shown that the only part of the protein affected by mutation is the reasonably rearranged hydrophobic core. It is hence concluded that stabilisation energies, which are dominated by London dispersion, represent the main source of stability of this protein.

Návaznosti

LC06030, projekt VaV
Název: Biomolekulární centrum
Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Biomolekulární centrum
MSM0021622413, záměr
Název: Proteiny v metabolismu a při interakci organismů s prostředím
Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Proteiny v metabolismu a při interakci organismů s prostředím