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Titolo:
Cavity-filling mutations enhance protein stability by lowering the free energy of native state
Autore:
Saito, M; Kono, H; Morii, H; Uedaira, H; Tahirov, TH; Ogata, K; Sarai, A;
Indirizzi:
Hirosaki Univ, Fac Sci & Technol, Hirosaki, Aomori 0368561, Japan HirosakiUniv Hirosaki Aomori Japan 0368561 rosaki, Aomori 0368561, Japan Inst Phys & Chem Res, Tsukuba Life Sci Ctr, Tsukuba, Ibaraki 3050074, Japan Inst Phys & Chem Res Tsukuba Ibaraki Japan 3050074 Ibaraki 3050074, Japan Natl Inst Biosci & Human Technol, Tsukuba, Ibaraki 3058566, Japan Natl Inst Biosci & Human Technol Tsukuba Ibaraki Japan 3058566 566, Japan Kanagawa Acad Sci & Technol, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan Kanagawa Acad Sci & Technol Yokohama Kanagawa Japan 2360004 360004, Japan Yokohama City Univ, Sch Med, Dept Biol Struct, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan Yokohama City Univ Yokohama Kanagawa Japan 2360004 anagawa 2360004, Japan
Titolo Testata:
JOURNAL OF PHYSICAL CHEMISTRY B
fascicolo: 15, volume: 104, anno: 2000,
pagine: 3705 - 3711
SICI:
1520-6106(20000420)104:15<3705:CMEPSB>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
DNA-BINDING DOMAIN; MOLECULAR-DYNAMICS SIMULATIONS; RANGE COULOMB INTERACTIONS; ACID SIDE-CHAINS; HUMAN LYSOZYME; THERMODYNAMIC DECOMPOSITION; THERMAL-STABILITY; HYDROPHOBIC CORE; RIBONUCLEASE HI; NUCLEIC-ACIDS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Physical, Chemical & Earth Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Saito, M Hirosaki Univ, Fac Sci & Technol, 3 Bunkyo Cho, Hirosaki, Aomori 0368561, Japan Hirosaki Univ 3 Bunkyo Cho Hirosaki Aomori Japan 0368561 1, Japan
Citazione:
M. Saito et al., "Cavity-filling mutations enhance protein stability by lowering the free energy of native state", J PHYS CH B, 104(15), 2000, pp. 3705-3711

Abstract

The stabilization of proteins due to cavity-filling mutations are thought to be attributable to removal of hydrophobic residues from solvent exposurein denatured (D) state and formation of close packing in native (N) state. However, it is still unclear which contribution is dominant to stabilize proteins, because experiments can probe only the free energy difference between the two states (N and D). To address this question, we carried out molecular dynamics simulations, circular dichroism (CD) measurements, and X-raycrystallographic experiments on the cavity-filling mutations of the DNA-binding domain of the Myb transcriptional regulator. The cavity size was altered by systematic natural and nonnatural amino acid substitutions at a fixed site. The stability free energy change (Delta Delta G(N-->D;W-->M)) and the cavity-size change (Delta V) calculated for the mutations agreed with the experimental data observed by urea-titration/CD measurements and crystallographic structure analysis, respectively. We found that the experimental Delta Delta G values correlate well with the calculated native-state free energy change due to mutations Delta G(N;W-->M) and with Delta V(their correlation coefficients are larger than 0.9) but not with the denatured-state Delta G(D;W-->M). These results demonstrated that the decrease in cavity sizeincreases the protein stability by lowering the free energy of native state for this protein. We discussed physicochemical meanings of our calculation results for Delta G(N;W-->M) and Delta G(D;W-->M).

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Documento generato il 10/07/20 alle ore 00:18:59