دورية أكاديمية
Quantifying tetrahedral adduct formation and stabilization in the cysteine and the serine proteases.
| العنوان: | Quantifying tetrahedral adduct formation and stabilization in the cysteine and the serine proteases. |
|---|---|
| المؤلفون: | Cleary JA; School of Biomolecular and Biomedical Science, Centre for Synthesis and Chemical Biology, Conway Institute, University College Dublin, Dublin 4, Ireland., Doherty W; School of Chemistry, Centre for Synthesis and Chemical Biology, Conway Institute, University College Dublin, Dublin 4, Ireland., Evans P; School of Chemistry, Centre for Synthesis and Chemical Biology, Conway Institute, University College Dublin, Dublin 4, Ireland., Malthouse JP; School of Biomolecular and Biomedical Science, Centre for Synthesis and Chemical Biology, Conway Institute, University College Dublin, Dublin 4, Ireland. Electronic address: J.Paul.G.Malthouse@ucd.ie. |
| المصدر: | Biochimica et biophysica acta [Biochim Biophys Acta] 2015 Oct; Vol. 1854 (10 Pt A), pp. 1382-91. Date of Electronic Publication: 2015 Jul 11. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Pub. Co Country of Publication: Netherlands NLM ID: 0217513 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0006-3002 (Print) Linking ISSN: 00063002 NLM ISO Abbreviation: Biochim Biophys Acta Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam : Elsevier Pub. Co. |
| مواضيع طبية MeSH: | Chymotrypsin/*chemistry , Cysteine Proteinase Inhibitors/*chemistry , Dipeptides/*chemistry , Papain/*chemistry , Serine Proteinase Inhibitors/*chemistry, Chymotrypsin/antagonists & inhibitors ; Humans ; Hydrogen Bonding ; Kinetics ; Papain/antagonists & inhibitors ; Protein Stability ; Recombinant Proteins/chemistry ; Structure-Activity Relationship |
| مستخلص: | Two new papain inhibitors have been synthesized where the terminal α-carboxyl groups of Z-Phe-Ala-COOH and Ac-Phe-Gly-COOH have been replaced by a proton to give Z-Phe-Ala-H and Ac-Phe-Gly-H. We show that for papain, replacing the terminal carboxylate group of a peptide inhibitor with a hydrogen atom decreases binding 3-4 fold while replacing an aldehyde or glyoxal group with a hydrogen atom decreases binding by 300,000-1,000,000 fold. Thiohemiacetal formation by papain with aldehyde or glyoxal inhibitors is shown to be ~10,000 times more effective than hemiacetal or hemiketal formation with chymotrypsin. It is shown using effective molarities, that for papain, thiohemiacetal stabilization is more effective with aldehyde inhibitors than with glyoxal inhibitors. The effective molarity obtained when papain is inhibited by an aldehyde inhibitor is similar to the effective molarity obtained when chymotrypsin is inhibited by glyoxal inhibitors showing that both enzymes can stabilize tetrahedral adducts by similar amounts. Therefore the greater potency of aldehyde and glyoxal inhibitors with papain is not due to greater thiohemiacetal stabilization by papain compared to the hemiketal and hemiacetal stabilization by chymotrypsin, instead it reflects the greater intrinsic reactivity of the catalytic thiol group of papain compared to the catalytic hydroxyl group of chymotrypsin. It is argued that while the hemiacetals and thiohemiacetals formed with the serine and cysteine proteases respectively can mimic the catalytic tetrahedral intermediate they are also analogues of the productive and non-productive acyl intermediates that can be formed with the cysteine and serine proteases. (Copyright © 2015. Published by Elsevier B.V.) |
| References: | J Am Chem Soc. 1973 Feb 7;95(3):875-9. (PMID: 4688657) Antiviral Res. 2011 Nov;92(2):204-12. (PMID: 21854807) Acta Crystallogr D Biol Crystallogr. 2000 Mar;56(Pt 3):280-6. (PMID: 10713514) Eur J Biochem. 1977 Sep 15;79(1):201-9. (PMID: 913417) Biochemistry. 1985 Jul 2;24(14):3478-87. (PMID: 4041423) Biochemistry. 1986 Apr 22;25(8):2293-8. (PMID: 3707946) Biochem J. 1997 Sep 15;326 ( Pt 3):861-6. (PMID: 9307038) Arch Biochem Biophys. 1961 Nov;95:271-8. (PMID: 13890599) Biochemistry. 1990 May 22;29(20):4871-9. (PMID: 2364065) FEBS J. 2005 Jan;272(2):562-72. (PMID: 15654893) J Biol Chem. 1977 Oct 10;252(19):6776-82. (PMID: 893442) Biochemistry. 1985 Jan 29;24(3):606-9. (PMID: 3888259) FEBS Lett. 1993 Jan 2;315(1):38-42. (PMID: 8416808) J Med Chem. 1998 Nov 5;41(23):4567-76. (PMID: 9804696) PLoS One. 2013 Sep 02;8(9):e73530. (PMID: 24023882) J Mol Biol. 2009 Feb 6;385(5):1568-77. (PMID: 19059417) J Biol Chem. 1991 Jun 25;266(18):11797-800. (PMID: 1904870) Biochim Biophys Acta. 1994 Dec 15;1201(3):447-53. (PMID: 7803476) J Med Chem. 2011 Dec 8;54(23):7962-73. (PMID: 22014094) Biochim Biophys Acta. 2014 Jun;1844(6):1119-27. (PMID: 24657307) J Med Chem. 1998 Jul 16;41(15):2786-805. (PMID: 9667969) Biochem J. 2002 Sep 15;366(Pt 3):983-7. (PMID: 12061892) J Struct Biol. 2011 Jan;173(1):14-9. (PMID: 20850545) Biochemistry. 1983 Jan 4;22(1):117-22. (PMID: 6338911) Biochem J. 1978 Jul 1;173(1):345-7. (PMID: 687376) Biochemistry. 1973 Feb 27;12(5):816-22. (PMID: 4686799) J Mol Biol. 1980 May 5;139(1):45-51. (PMID: 6790710) Biochemistry. 2007 Nov 6;46(44):12868-74. (PMID: 17927215) Biochim Biophys Acta. 2005 May 20;1749(1):33-41. (PMID: 15848134) J Mol Biol. 1985 May 5;183(1):89-103. (PMID: 3892018) Biochim Biophys Acta. 1991 Jan 23;1073(1):33-42. (PMID: 1991144) Biochemistry. 1995 Jan 17;34(2):464-71. (PMID: 7819238) J Mol Biol. 1970 Dec 14;54(2):341-54. (PMID: 5494034) Biochemistry. 1989 Aug 22;28(17):7033-8. (PMID: 2819046) J Mol Biol. 1980 Nov 25;144(1):43-88. (PMID: 6783761) Biochemistry. 1972 Nov 7;11(23):4293-303. (PMID: 5079900) J Mol Biol. 1994 Aug 26;241(4):574-87. (PMID: 8057380) J Biol Chem. 2007 Mar 16;282(11):7852-61. (PMID: 17213185) J Virol. 2013 Apr;87(8):4281-92. (PMID: 23365454) Biochemistry. 2012 Aug 7;51(31):6164-70. (PMID: 22757750) Biochem J. 1993 Jul 15;293 ( Pt 2):321-3. (PMID: 8343111) Biochemistry. 1991 Oct 15;30(41):10026-34. (PMID: 1911768) Biochemistry. 1981 Sep 15;20(19):5517-24. (PMID: 7295689) Biochemistry. 1976 Aug 24;15(17):3731-8. (PMID: 952885) Biochemistry. 1995 Jun 27;34(25):8172-9. (PMID: 7794931) Biochem J. 2002 Mar 1;362(Pt 2):339-47. (PMID: 11853541) Biochem J. 1973 Jul;133(3):573-84. (PMID: 4733241) Org Lett. 2003 Mar 6;5(5):737-40. (PMID: 12605503) Biochemistry. 1991 Sep 17;30(37):8924-8. (PMID: 1892809) Protein Sci. 1996 Apr;5(4):752-8. (PMID: 8845765) J Biol Chem. 2002 Jun 14;277(24):21962-70. (PMID: 11896054) J Biol Chem. 1972 Dec 25;247(24):8195-7. (PMID: 4640942) Biochim Biophys Acta. 2009 Aug;1794(8):1251-8. (PMID: 19393346) Biochem J. 1985 Apr 15;227(2):521-8. (PMID: 3890831) |
| فهرسة مساهمة: | Keywords: Aldehyde inhibitor; Cysteine protease; Glyoxal inhibitor; Serine protease; Tetrahedral intermediate |
| المشرفين على المادة: | 0 (Cysteine Proteinase Inhibitors) 0 (Dipeptides) 0 (Recombinant Proteins) 0 (Serine Proteinase Inhibitors) 16088-00-9 (N-benzyloxycarbonylphenylalanylalanine) 73392-20-8 (acetylphenylalanylglycinal) EC 3.4.21.1 (Chymotrypsin) EC 3.4.22.2 (Papain) |
| تواريخ الأحداث: | Date Created: 20150715 Date Completed: 20151201 Latest Revision: 20220216 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC7185411 |
| DOI: | 10.1016/j.bbapap.2015.07.006 |
| PMID: | 26169698 |
| قاعدة البيانات: | MEDLINE |
كن أول من يترك تعليقا!