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Triosephosphate Isomerase: The Crippling Effect of the P168A/I172A Substitution at the Heart of an Enzyme Active Site.

التفاصيل البيبلوغرافية
العنوان: Triosephosphate Isomerase: The Crippling Effect of the P168A/I172A Substitution at the Heart of an Enzyme Active Site.
المؤلفون: Hegazy R; Department of Chemistry, University at Buffalo, SUNY, Buffalo, New York 14260-3000, United States., Richard JP; Department of Chemistry, University at Buffalo, SUNY, Buffalo, New York 14260-3000, United States.
المصدر: Biochemistry [Biochemistry] 2023 Oct 17; Vol. 62 (20), pp. 2916-2927. Date of Electronic Publication: 2023 Sep 28.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: American Chemical Society Country of Publication: United States NLM ID: 0370623 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-4995 (Electronic) Linking ISSN: 00062960 NLM ISO Abbreviation: Biochemistry Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, American Chemical Society.
مواضيع طبية MeSH: Triose-Phosphate Isomerase*/chemistry , Glyceraldehyde 3-Phosphate*/chemistry, Catalytic Domain ; Catalysis
مستخلص: The P168 and I172 side chains sit at the heart of the active site of triosephosphate isomerase (TIM) and play important roles in the catalysis of the isomerization reaction. The phosphodianion of substrate glyceraldehyde 3-phosphate (GAP) drives a conformational change at the TIM that creates a steric interaction with the P168 side chain that is relieved by the movement of P168 that carries the basic E167 side chain into a clamp that consists of the hydrophobic I172 and L232 side chains. The P168A/I172A substitution at TIM from Trypanosoma brucei brucei ( Tbb TIM) causes a large 120,000-fold decrease in k cat for isomerization of GAP that eliminates most of the difference in the reactivity of TIM compared to the small amine base quinuclidinone for deprotonation of catalyst-bound GAP. The I172A substitution causes a > 2-unit decrease in the p K a of the E167 carboxylic acid in a complex to the intermediate analog PGA, but the P168A substitution at the I172A variant has no further effect on this p K a . The P168A/I172A substitutions cause a 5-fold decrease in K m for the isomerization of GAP from a 0.9 kcal/mol stabilization of the substrate Michaelis complexes. The results show that the P168 and I172 side chains play a dual role in destabilizing the ground-state Michaelis complex to GAP and in promoting stabilization of the transition state for substrate isomerization. This is consistent with an important role for these side chains in an induced fit reaction mechanism [Richard, J. P. (2022) Enabling Role of Ligand-Driven Conformational Changes in Enzyme Evolution. Biochemistry 61, 1533-1542].
References: J Am Chem Soc. 2015 Jan 28;137(3):1372-82. (PMID: 25555107)
Biochemistry. 2022 Aug 2;61(15):1533-1542. (PMID: 35829700)
J Am Chem Soc. 2012 Jun 20;134(24):10286-98. (PMID: 22583393)
Protein Eng Des Sel. 2004 Apr;17(4):375-82. (PMID: 15166315)
Biochemistry. 1988 Aug 9;27(16):5948-60. (PMID: 2847777)
Biochemistry. 2013 Mar 26;52(12):2021-35. (PMID: 23327224)
Philos Trans R Soc Lond B Biol Sci. 1991 May 29;332(1263):115-21. (PMID: 1678530)
Biochemistry. 2009 Jun 23;48(24):5769-78. (PMID: 19425580)
Adv Enzymol Relat Areas Mol Biol. 1975;43:219-410. (PMID: 892)
Biochemistry. 2023 Mar 7;62(5):969-970. (PMID: 36791154)
Biochemistry. 2015 Jul 28;54(29):4555-64. (PMID: 26135041)
Biochemistry. 2023 Jun 6;62(11):1794-1806. (PMID: 37162263)
Biochemistry. 1993 Nov 16;32(45):11943-52. (PMID: 8218268)
J Am Chem Soc. 2001 Nov 14;123(45):11325-6. (PMID: 11697989)
J Mol Biol. 2007 Apr 20;368(1):131-49. (PMID: 17336327)
J Am Chem Soc. 2014 Jul 16;136(28):10156-65. (PMID: 24958125)
Biochemistry. 2007 May 15;46(19):5841-54. (PMID: 17444661)
Biochemistry. 2013 Aug 27;52(34):5928-40. (PMID: 23909928)
Curr Opin Struct Biol. 2010 Dec;20(6):702-10. (PMID: 20951028)
Protein Eng Des Sel. 2017 Mar 1;30(3):157-165. (PMID: 27903763)
J Am Chem Soc. 2019 Feb 27;141(8):3320-3331. (PMID: 30703322)
Biochemistry. 1994 Mar 15;33(10):2830-7. (PMID: 8130195)
Biochemistry. 2004 Sep 14;43(36):11436-45. (PMID: 15350130)
Biochemistry. 1992 Sep 15;31(36):8482-7. (PMID: 1390632)
Biochemistry. 2005 Feb 22;44(7):2610-21. (PMID: 15709774)
J Am Chem Soc. 2015 Dec 9;137(48):15185-97. (PMID: 26570983)
Biochem J. 1972 Sep;129(2):311-20. (PMID: 4643319)
Biochemistry. 1991 Jun 18;30(24):5821-6. (PMID: 2043623)
Biochemistry. 2011 Jun 28;50(25):5767-79. (PMID: 21553855)
Nucleic Acids Res. 2003 Jul 1;31(13):3784-8. (PMID: 12824418)
Biochem Biophys Res Commun. 1978 Jul 14;83(1):347-52. (PMID: 29623)
Biochemistry. 2012 Apr 3;51(13):2652-61. (PMID: 22409228)
Biochemistry. 2014 Jun 3;53(21):3486-501. (PMID: 24825099)
Biochem J. 1979 Jun 1;179(3):607-21. (PMID: 38777)
Biochemistry. 2006 Dec 26;45(51):15483-94. (PMID: 17176070)
Cell Mol Life Sci. 2010 Dec;67(23):3961-82. (PMID: 20694739)
Biochemistry. 2016 May 31;55(21):3036-47. (PMID: 27149328)
J Am Chem Soc. 2015 Apr 29;137(16):5312-5. (PMID: 25884759)
IUCrJ. 2021 Jun 03;8(Pt 4):633-643. (PMID: 34258011)
Biochemistry. 1975 Dec 2;14(24):5274-9. (PMID: 47)
Biochemistry. 1990 Apr 3;29(13):3186-94. (PMID: 2185832)
Curr Opin Chem Biol. 2014 Aug;21:1-10. (PMID: 24699188)
J Biol Chem. 2003 Mar 14;278(11):9544-51. (PMID: 12522213)
Proteins. 2017 Jul;85(7):1190-1211. (PMID: 28378917)
J Am Chem Soc. 2018 Jul 5;140(26):8277-8286. (PMID: 29862813)
Biochemistry. 1992 Sep 15;31(36):8488-94. (PMID: 1390633)
Biochemistry. 1988 Feb 23;27(4):1158-67. (PMID: 3365378)
Biochemistry. 2018 Jun 12;57(23):3227-3236. (PMID: 29337541)
Biochemistry. 1976 Dec 14;15(25):5627-31. (PMID: 999838)
J Phys Org Chem. 2014 Apr 1;27(4):269-276. (PMID: 24729658)
J Biol Chem. 1998 Oct 16;273(42):27035-8. (PMID: 9765214)
Proteins. 2006 Aug 15;64(3):700-10. (PMID: 16741995)
Eur J Biochem. 1993 Feb 1;211(3):703-10. (PMID: 8436128)
J Am Chem Soc. 2013 Apr 24;135(16):5978-81. (PMID: 23560625)
معلومات مُعتمدة: R35 GM134881 United States GM NIGMS NIH HHS
المشرفين على المادة: EC 5.3.1.1 (Triose-Phosphate Isomerase)
142-10-9 (Glyceraldehyde 3-Phosphate)
تواريخ الأحداث: Date Created: 20230928 Date Completed: 20231023 Latest Revision: 20231111
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC10586322
DOI: 10.1021/acs.biochem.3c00414
PMID: 37768194
قاعدة البيانات: MEDLINE
الوصف
تدمد:1520-4995
DOI:10.1021/acs.biochem.3c00414