亚胺培南作为β-内酰胺酶的底物和抑制剂。
Imipenem as substrate and inhibitor of beta-lactamases.
作者信息
Monks J, Waley S G
机构信息
Sir William Dunn School of Pathology, University of Oxford, U.K.
出版信息
Biochem J. 1988 Jul 15;253(2):323-8. doi: 10.1042/bj2530323.
Abstract
The interaction between imipenem, a carbapenem antibiotic, and two representative beta-lactamases has been studied. The first enzyme was beta-lactamase I, a class-A beta-lactamase from Bacillus cereus; imipenem behaved as a slow substrate (kcat. 6.7 min-1, Km 0.4 mM at 30 degrees C and at pH 7) that reacted by a branched pathway. There was transient formation of an altered species formed in a reversible reaction; this species was probably an acyl-enzyme in a slightly altered, but considerably more labile, conformation. The kinetics of the reaction were investigated by measuring both the concentration of the substrate and the activity of the enzyme, which fell and then rose again more slowly. The second enzyme was the chromosomal class-C beta-lactamase from Pseudomonas aeruginosa; imipenem was a substrate with a low kcat. (0.8 min-1) and a low Km (0.7 microM). Possible implications for the clinical use of imipenem are considered.
摘要
研究了碳青霉烯类抗生素亚胺培南与两种代表性β-内酰胺酶之间的相互作用。第一种酶是β-内酰胺酶I，一种来自蜡样芽孢杆菌的A类β-内酰胺酶；亚胺培南表现为一种缓慢底物（在30℃和pH 7条件下，kcat为6.7 min-1，Km为0.4 mM），通过分支途径反应。在可逆反应中短暂形成了一种改变的物种；该物种可能是一种构象略有改变但稳定性大大降低的酰基酶。通过测量底物浓度和酶活性来研究反应动力学，酶活性先下降然后又更缓慢地上升。第二种酶是铜绿假单胞菌的染色体C类β-内酰胺酶；亚胺培南是一种kcat较低（0.8 min-1）且Km较低（0.7 μM）的底物。文中考虑了亚胺培南临床应用的可能影响。
相似文献
1
Imipenem as substrate and inhibitor of beta-lactamases.亚胺培南作为β-内酰胺酶的底物和抑制剂。
Biochem J. 1988 Jul 15;253(2):323-8. doi: 10.1042/bj2530323.
2
Substrate-induced inactivation of the OXA2 beta-lactamase.底物诱导的OXA2β-内酰胺酶失活
Biochem J. 1993 Nov 1;295 ( Pt 3)(Pt 3):871-8. doi: 10.1042/bj2950871.
3
beta-Lactamase Id of ceftazidime-resistant Pseudomonas aeruginosa strains.耐头孢他啶铜绿假单胞菌菌株的β-内酰胺酶鉴定
Microbiologica. 1992 Jan;15(1):65-9.
4
Imipenem-Relebactam and Meropenem-Vaborbactam: Two Novel Carbapenem-β-Lactamase Inhibitor Combinations.亚胺培南-西司他丁钠和美罗培南-法硼巴坦：两种新型碳青霉烯-β-内酰胺酶抑制剂复方制剂。
Drugs. 2018 Jan;78(1):65-98. doi: 10.1007/s40265-017-0851-9.
5
A survey of the kinetic parameters of class C beta-lactamases. Cephalosporins and other beta-lactam compounds.C类β-内酰胺酶动力学参数的研究。头孢菌素及其他β-内酰胺类化合物。
Biochem J. 1988 Oct 1;255(1):123-9. doi: 10.1042/bj2550123.
6
Cryoenzymology of beta-lactamases.
Biochemistry. 1987 Aug 25;26(17):5329-37. doi: 10.1021/bi00391a017.
7
Oxacillin-hydrolyzing beta-lactamase involved in resistance to imipenem in Acinetobacter baumannii.鲍曼不动杆菌中参与对亚胺培南耐药的水解苯唑西林β-内酰胺酶
FEMS Microbiol Lett. 1997 Aug 15;153(2):333-9. doi: 10.1111/j.1574-6968.1997.tb12593.x.
8
Single-turnover and steady-state kinetics of hydrolysis of cephalosporins by beta-lactamase I from Bacillus cereus.蜡样芽孢杆菌β-内酰胺酶I催化头孢菌素水解的单周转和稳态动力学
Biochem J. 1985 Oct 1;231(1):83-8. doi: 10.1042/bj2310083.
9
Site-directed mutagenesis and substrate-induced inactivation of beta-lactamase I.β-内酰胺酶I的定点诱变与底物诱导失活
Biochem J. 1992 Dec 15;288 ( Pt 3)(Pt 3):1045-51. doi: 10.1042/bj2881045.
10
The pH-dependence of class B and class C beta-lactamases.B类和C类β-内酰胺酶的pH依赖性
Biochem J. 1983 Jul 1;213(1):61-6. doi: 10.1042/bj2130061.
引用本文的文献
1
KPC-2 β-lactamase enables carbapenem antibiotic resistance through fast deacylation of the covalent intermediate.KPC-2 β-内酰胺酶通过快速脱去共价中间体的酰基而使碳青霉烯类抗生素产生耐药性。
J Biol Chem. 2021 Jan-Jun;296:100155. doi: 10.1074/jbc.RA120.015050. Epub 2020 Dec 10.
2
Structural Analysis of The OXA-48 Carbapenemase Bound to A "Poor" Carbapenem Substrate, Doripenem.与“劣质”碳青霉烯类底物多利培南结合的OXA-48碳青霉烯酶的结构分析
Antibiotics (Basel). 2019 Sep 11;8(3):145. doi: 10.3390/antibiotics8030145.
3
A kinetic analysis of the inhibition of FOX-4 β-lactamase, a plasmid-mediated AmpC cephalosporinase, by monocyclic β-lactams and carbapenems.单环β-内酰胺类和碳青霉烯类对质粒介导的AmpC头孢菌素酶FOX-4β-内酰胺酶抑制作用的动力学分析
J Antimicrob Chemother. 2014 Mar;69(3):682-90. doi: 10.1093/jac/dkt434. Epub 2013 Nov 13.
4
Targeting the cell wall of Mycobacterium tuberculosis: structure and mechanism of L,D-transpeptidase 2.靶向结核分枝杆菌细胞壁：L，D-转肽酶 2 的结构与机制。
Structure. 2012 Dec 5;20(12):2103-15. doi: 10.1016/j.str.2012.09.016. Epub 2012 Oct 25.
5
Carbapenems: past, present, and future.碳青霉烯类抗生素：过去、现在和未来。
Antimicrob Agents Chemother. 2011 Nov;55(11):4943-60. doi: 10.1128/AAC.00296-11. Epub 2011 Aug 22.
6
Three decades of beta-lactamase inhibitors.三十年的β-内酰胺酶抑制剂。
Clin Microbiol Rev. 2010 Jan;23(1):160-201. doi: 10.1128/CMR.00037-09.
7
Inhibition of the class C beta-lactamase from Acinetobacter spp.: insights into effective inhibitor design.抑制不动杆菌属的 C 类β-内酰胺酶：有效抑制剂设计的见解。
Biochemistry. 2010 Jan 19;49(2):329-40. doi: 10.1021/bi9015988.
8
Inhibition of class A beta-lactamases by carbapenems: crystallographic observation of two conformations of meropenem in SHV-1.碳青霉烯类对A类β-内酰胺酶的抑制作用：美罗培南在SHV-1中两种构象的晶体学观察
J Am Chem Soc. 2008 Sep 24;130(38):12656-62. doi: 10.1021/ja7111146. Epub 2008 Aug 30.
9
OXA-18, a class D clavulanic acid-inhibited extended-spectrum beta-lactamase from Pseudomonas aeruginosa.OXA-18，一种来自铜绿假单胞菌的D类克拉维酸抑制型超广谱β-内酰胺酶。
Antimicrob Agents Chemother. 1997 Oct;41(10):2188-95. doi: 10.1128/AAC.41.10.2188.
10
Characterization of a novel extended-spectrum beta-lactamase from Pseudomonas aeruginosa.铜绿假单胞菌新型超广谱β-内酰胺酶的特性分析
Antimicrob Agents Chemother. 1993 May;37(5):962-9. doi: 10.1128/AAC.37.5.962.
本文引用的文献
1
A quick method for the determination of inhibition constants.一种测定抑制常数的快速方法。
Biochem J. 1982 Sep 1;205(3):631-3. doi: 10.1042/bj2050631.
2
Inhibition of the RTEM beta-lactamase from Escherichia coli. Interaction of the enzyme with derivatives of olivanic acid.大肠杆菌RTEMβ-内酰胺酶的抑制作用。该酶与橄榄酸衍生物的相互作用。
Biochemistry. 1982 Jun 8;21(12):2857-62. doi: 10.1021/bi00541a008.
3
Inhibition of the RTEM beta-lactamase from Escherichia coli. Interaction of enzyme with derivatives of olivanic acid.
Biochemistry. 1981 May 12;20(10):2732-7. doi: 10.1021/bi00513a005.
4
Purification and properties of inducible penicillin beta-lactamase isolated from Pseudomonas maltophilia.从嗜麦芽窄食单胞菌中分离出的诱导型青霉素β-内酰胺酶的纯化及特性
Antimicrob Agents Chemother. 1982 Oct;22(4):564-70. doi: 10.1128/AAC.22.4.564.
5
Interaction between serine beta-lactamases and class A substrates: a kinetic analysis and a reaction pathway hypothesis.丝氨酸β-内酰胺酶与A类底物之间的相互作用：动力学分析及反应途径假说
Biochem Pharmacol. 1981 Mar 15;30(6):549-52. doi: 10.1016/0006-2952(81)90124-6.
6
The acyl-enzyme mechanism of beta-lactamase action. The evidence for class C Beta-lactamases.β-内酰胺酶作用的酰基-酶机制。C类β-内酰胺酶的证据。
Biochem J. 1982 Nov 1;207(2):315-22. doi: 10.1042/bj2070315.
7
Permeability of Pseudomonas aeruginosa outer membrane to hydrophilic solutes.铜绿假单胞菌外膜对亲水性溶质的通透性。
J Bacteriol. 1982 Nov;152(2):636-42. doi: 10.1128/jb.152.2.636-642.1982.
8
Active sites of beta-lactamases. The chromosomal beta-lactamases of Pseudomonas aeruginosa and Escherichia coli.β-内酰胺酶的活性位点。铜绿假单胞菌和大肠杆菌的染色体β-内酰胺酶。
Biochem J. 1982 Mar 1;201(3):621-7. doi: 10.1042/bj2010621.
9
Isolation and properties of an inducible and a constitutive beta-lactamase from Pseudomonas aeruginosa.铜绿假单胞菌中一种诱导型和一种组成型β-内酰胺酶的分离与特性
J Gen Microbiol. 1982 Jan;128(1):155-9. doi: 10.1099/00221287-128-1-155.
10
ampC cephalosporinase of Escherichia coli K-12 has a different evolutionary origin from that of beta-lactamases of the penicillinase type.大肠杆菌K-12的AmpC头孢菌素酶与青霉素酶型β-内酰胺酶有着不同的进化起源。
Proc Natl Acad Sci U S A. 1981 Aug;78(8):4897-901. doi: 10.1073/pnas.78.8.4897.
Zotero 插件