丝氨酸235通过关键氢键作用对TEM-1β-内酰胺酶的头孢菌素酶活性发挥作用。
Critical hydrogen bonding by serine 235 for cephalosporinase activity of TEM-1 beta-lactamase.
作者信息
Imtiaz U, Manavathu E K, Lerner S A, Mobashery S
机构信息
Department of Chemistry, Wayne State University, Detroit, Michigan 48202.
出版信息
Antimicrob Agents Chemother. 1993 Nov;37(11):2438-42. doi: 10.1128/AAC.37.11.2438.
Abstract
The role of Ser-235 in the catalytic mechanism of the TEM-1 beta-lactamase has been explored by the study of a mutant enzyme in which Ser-235 has been substituted by alanine (Ala-235 mutant enzyme). A comparative kinetic analysis of both the wild-type and the Ala-235 TEM-1 enzymes revealed little effect of this substitution of residue 235 on the turnover of penicillins but a greater effect on the turnover of cephalosporins. Susceptibility testing of Escherichia coli strains harboring the wild-type TEM-1 beta-lactamase and the Ala-235 mutant enzyme revealed an effect of the mutation similar to that observed in the enzymological studies. The MICs of two representative cephalosporins for the strain containing the mutant enzyme were much lower than those for the isogenic strain bearing the wild-type TEM-1 beta-lactamase. On the other hand, the strain with the mutant enzyme was still highly resistant to penicillins.
摘要
通过对一种突变酶（其中Ser-235被丙氨酸取代的Ala-235突变酶）的研究，探索了Ser-235在TEM-1β-内酰胺酶催化机制中的作用。对野生型和Ala-235 TEM-1酶进行的比较动力学分析表明，235位残基的这种取代对青霉素的周转影响不大，但对头孢菌素的周转影响较大。对携带野生型TEM-1β-内酰胺酶和Ala-235突变酶的大肠杆菌菌株进行的药敏试验显示，该突变的影响与酶学研究中观察到的相似。两种代表性头孢菌素对含有突变酶的菌株的最低抑菌浓度远低于携带野生型TEM-1β-内酰胺酶的同基因菌株。另一方面，含有突变酶的菌株对青霉素仍具有高度抗性。
相似文献
1
Critical hydrogen bonding by serine 235 for cephalosporinase activity of TEM-1 beta-lactamase.丝氨酸235通过关键氢键作用对TEM-1β-内酰胺酶的头孢菌素酶活性发挥作用。
Antimicrob Agents Chemother. 1993 Nov;37(11):2438-42. doi: 10.1128/AAC.37.11.2438.
2
Extension of resistance to cefepime and cefpirome associated to a six amino acid deletion in the H-10 helix of the cephalosporinase of an Enterobacter cloacae clinical isolate.阴沟肠杆菌临床分离株头孢菌素酶H-10螺旋中六个氨基酸缺失导致对头孢吡肟和头孢匹罗耐药性的扩展。
FEMS Microbiol Lett. 2001 Feb 20;195(2):185-90. doi: 10.1111/j.1574-6968.2001.tb10519.x.
3
Catalytic mechanism of active-site serine beta-lactamases: role of the conserved hydroxy group of the Lys-Thr(Ser)-Gly triad.活性位点丝氨酸β-内酰胺酶的催化机制：赖氨酸-苏氨酸（丝氨酸）-甘氨酸三联体中保守羟基的作用。
Biochem J. 1994 Jul 15;301 ( Pt 2)(Pt 2):485-94. doi: 10.1042/bj3010485.
4
Extension of the substrate spectrum by an amino acid substitution at residue 219 in the Citrobacter freundii cephalosporinase.弗氏柠檬酸杆菌头孢菌素酶中第219位残基的氨基酸取代对底物谱的扩展
J Bacteriol. 1990 Aug;172(8):4348-51. doi: 10.1128/jb.172.8.4348-4351.1990.
5
A triple mutant in the Ω-loop of TEM-1 β-lactamase changes the substrate profile via a large conformational change and an altered general base for catalysis.TEM-1 β-内酰胺酶Ω环中的三重突变通过大的构象变化和改变催化的通用碱来改变底物谱。
J Biol Chem. 2015 Apr 17;290(16):10382-94. doi: 10.1074/jbc.M114.633438. Epub 2015 Feb 20.
6
Cloning and expression of a cloxacillin-hydrolyzing enzyme and a cephalosporinase from Aeromonas sobria AER 14M in Escherichia coli: requirement for an E. coli chromosomal mutation for efficient expression of the class D enzyme.嗜水气单胞菌AER 14M中一种氯唑西林水解酶和一种头孢菌素酶在大肠杆菌中的克隆与表达：D类酶高效表达对大肠杆菌染色体突变的需求
Antimicrob Agents Chemother. 1994 Sep;38(9):2078-85. doi: 10.1128/AAC.38.9.2078.
7
Naturally occurring extended-spectrum cephalosporinases in Escherichia coli.大肠杆菌中天然存在的超广谱头孢菌素酶
Antimicrob Agents Chemother. 2006 Jul;50(7):2573-6. doi: 10.1128/AAC.01633-05.
8
Elucidation of the role of arginine-244 in the turnover processes of class A beta-lactamases.
Biochemistry. 1992 Apr 21;31(15):3847-52. doi: 10.1021/bi00130a016.
9
Substitution of Met-69 by Ala or Gly in TEM-1 beta-lactamase confer an increased susceptibility to clavulanic acid and other inhibitors.在TEM-1β-内酰胺酶中，将第69位的甲硫氨酸替换为丙氨酸或甘氨酸会增加对克拉维酸和其他抑制剂的敏感性。
FEMS Microbiol Lett. 2002 May 21;211(1):13-6. doi: 10.1111/j.1574-6968.2002.tb11196.x.
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.
引用本文的文献
1
Unraveling the energetic significance of chemical events in enzyme catalysis via machine-learning based regression approach.通过基于机器学习的回归方法揭示酶催化中化学事件的能量学意义。
Commun Chem. 2020 Oct 8;3(1):134. doi: 10.1038/s42004-020-00379-w.
2
Three new inhibitors of class A β-lactamases evaluated by molecular docking and dynamics simulations methods: relebactam, enmetazobactam, and QPX7728.三种新型 A 类β-内酰胺酶抑制剂的分子对接和动力学模拟方法评价：雷利巴坦、恩他唑巴坦和 QPX7728。
J Mol Model. 2022 Mar 4;28(4):76. doi: 10.1007/s00894-022-05073-3.
3
In vivo functional analysis of a class A β-lactamase-related protein essential for clavulanic acid biosynthesis in Streptomyces clavuligerus.在体内对一株棒状链霉菌β-内酰胺酶相关蛋白进行功能分析，该蛋白对克拉维酸生物合成至关重要。
PLoS One. 2019 Apr 23;14(4):e0215960. doi: 10.1371/journal.pone.0215960. eCollection 2019.
4
The Drug-Resistant Variant P167S Expands the Substrate Profile of CTX-M β-Lactamases for Oxyimino-Cephalosporin Antibiotics by Enlarging the Active Site upon Acylation.耐药变体P167S通过在酰化时扩大活性位点来扩展CTX-Mβ-内酰胺酶对氧亚氨基头孢菌素抗生素的底物谱。
Biochemistry. 2017 Jul 11;56(27):3443-3453. doi: 10.1021/acs.biochem.7b00176. Epub 2017 Jun 27.
5
The Streptomyces-produced antibiotic fosfomycin is a promiscuous substrate for archaeal isopentenyl phosphate kinase.链霉菌产生的抗生素磷霉素是一种对古菌异戊烯磷酸激酶有广泛亲和性的底物。
Biochemistry. 2012 Jan 31;51(4):917-25. doi: 10.1021/bi201662k. Epub 2012 Jan 11.
6
Characterization of the inhibitor-resistant SHV β-lactamase SHV-107 in a clinical Klebsiella pneumoniae strain coproducing GES-7 enzyme.在一株同时产生 GES-7 酶的临床克雷伯氏肺炎菌中对抑制剂耐药的 SHVβ-内酰胺酶 SHV-107 的特性分析。
Antimicrob Agents Chemother. 2012 Feb;56(2):1042-6. doi: 10.1128/AAC.01444-10. Epub 2011 Nov 14.
7
KINARI-Web: a server for protein rigidity analysis.KINARI-Web：一个用于蛋白质刚性分析的服务器。
Nucleic Acids Res. 2011 Jul;39(Web Server issue):W177-83. doi: 10.1093/nar/gkr482. Epub 2011 Jun 21.
8
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.
9
Crystal structure and activity studies of the Mycobacterium tuberculosis beta-lactamase reveal its critical role in resistance to beta-lactam antibiotics.结核分枝杆菌β-内酰胺酶的晶体结构与活性研究揭示了其在对β-内酰胺类抗生素耐药性中的关键作用。
Antimicrob Agents Chemother. 2006 Aug;50(8):2762-71. doi: 10.1128/AAC.00320-06.
10
Probing substrate binding to metallo-beta-lactamase L1 from Stenotrophomonas maltophilia by using site-directed mutagenesis.通过定点诱变探究嗜麦芽窄食单胞菌金属β-内酰胺酶L1与底物的结合
BMC Biochem. 2002;3:4. doi: 10.1186/1471-2091-3-4. Epub 2002 Feb 13.
本文引用的文献
1
beta-Lactamase proceeds via an acyl-enzyme intermediate. Interaction of the Escherichia coli RTEM enzyme with cefoxitin.β-内酰胺酶通过酰基酶中间体起作用。大肠杆菌RTEM酶与头孢西丁的相互作用。
Biochemistry. 1980 Jun 24;19(13):2895-901. doi: 10.1021/bi00554a012.
2
Augmentin (amoxycillin and clavulanic acid) therapy in complicated infections due to beta-lactamase producing bacteria.阿莫西林克拉维酸钾（安灭菌）治疗产β-内酰胺酶细菌引起的复杂感染。
J Antimicrob Chemother. 1981 Mar;7(3):229-36. doi: 10.1093/jac/7.3.229.
3
Rapid and efficient site-specific mutagenesis without phenotypic selection.无需表型筛选的快速高效位点特异性诱变。
Proc Natl Acad Sci U S A. 1985 Jan;82(2):488-92. doi: 10.1073/pnas.82.2.488.
4
Single-stranded DNA 'blue' T7 promoter plasmids: a versatile tandem promoter system for cloning and protein engineering.单链DNA“蓝色”T7启动子质粒：一种用于克隆和蛋白质工程的通用串联启动子系统。
Protein Eng. 1986 Oct-Nov;1(1):67-74. doi: 10.1093/protein/1.1.67.
5
The crystal structure of the beta-lactamase of Streptomyces albus G at 0.3 nm resolution.白色链霉菌G的β-内酰胺酶在0.3纳米分辨率下的晶体结构。
Biochem J. 1987 Aug 1;245(3):911-3. doi: 10.1042/bj2450911.
6
Rapid and efficient site-specific mutagenesis without phenotypic selection.无需表型选择的快速高效位点特异性诱变。
Methods Enzymol. 1987;154:367-82. doi: 10.1016/0076-6879(87)54085-x.
7
Production of single-stranded plasmid DNA.单链质粒DNA的制备。
Methods Enzymol. 1987;153:3-11. doi: 10.1016/0076-6879(87)53044-0.
8
Tinkering with enzymes: what are we learning?对酶进行调整：我们学到了什么？
Science. 1987 Jun 5;236(4806):1252-8. doi: 10.1126/science.3296192.
9
Bacterial resistance to beta-lactam antibiotics: crystal structure of beta-lactamase from Staphylococcus aureus PC1 at 2.5 A resolution.细菌对β-内酰胺抗生素的耐药性：金黄色葡萄球菌PC1的β-内酰胺酶在2.5埃分辨率下的晶体结构。
Science. 1987 May 8;236(4802):694-701. doi: 10.1126/science.3107125.
10
Beta-lactamase of Bacillus licheniformis 749/C at 2 A resolution.地衣芽孢杆菌749/C的β-内酰胺酶，分辨率为2埃。
Proteins. 1990;7(2):156-71. doi: 10.1002/prot.340070205.
Zotero 插件