白色链霉菌G丝氨酸β-内酰胺酶。通过突变酶的分子建模探究催化机制。
Streptomyces albus G serine beta-lactamase. Probing of the catalytic mechanism via molecular modelling of mutant enzymes.
作者信息
Lamotte-Brasseur J, Jacob-Dubuisson F, Dive G, Frère J M, Ghuysen J M
机构信息
Centre d'Ingénierie des Protéines, Université de Liège, Sart tilman, Belgium.
出版信息
Biochem J. 1992 Feb 15;282 ( Pt 1)(Pt 1):189-95. doi: 10.1042/bj2820189.
Abstract
In previous studies, several amino acids of the active site of class A beta-lactamases have been modified by site-directed mutagenesis. On the basis of the catalytic mechanism proposed for the Streptomyces albus G beta-lactamase [Lamotte-Brasseur, Dive, Dideberg, Charlier, Frère & Ghuysen (1991) Biochem. J. 279, 213-221], the influence that these mutations exert on the hydrogen-bonding network of the active site has been analysed by molecular mechanics. The results satisfactorily explain the effects of the mutations on the kinetic parameters of the enzyme's activity towards a set of substrates. The present study also shows that, upon binding a properly structured beta-lactam compound, the impaired cavity of a mutant enzyme can readopt a functional hydrogen-bonding-network configuration.
摘要
在先前的研究中，通过定点诱变对A类β-内酰胺酶活性位点的几种氨基酸进行了修饰。基于为白色链霉菌Gβ-内酰胺酶提出的催化机制[拉莫特-布拉瑟尔、迪夫、迪德伯格、沙利耶、弗雷尔和居伊森（1991年）《生物化学杂志》279卷，213 - 221页]，通过分子力学分析了这些突变对活性位点氢键网络的影响。结果令人满意地解释了这些突变对该酶针对一组底物的活性动力学参数的影响。本研究还表明，在结合结构合适的β-内酰胺化合物时，突变酶受损的腔可以重新采用功能性氢键网络构型。
相似文献
1
Streptomyces albus G serine beta-lactamase. Probing of the catalytic mechanism via molecular modelling of mutant enzymes.白色链霉菌G丝氨酸β-内酰胺酶。通过突变酶的分子建模探究催化机制。
Biochem J. 1992 Feb 15;282 ( Pt 1)(Pt 1):189-95. doi: 10.1042/bj2820189.
2
The exocellular beta-lactamase of Streptomyces albus G. Purification, properties and comparison with the exocellular DD-carboxypeptidase.白色链霉菌G的胞外β-内酰胺酶。纯化、性质及与胞外DD-羧肽酶的比较。
Biochem J. 1981 Jan 1;193(1):75-82. doi: 10.1042/bj1930075.
3
Active-site serine mutants of the Streptomyces albus G beta-lactamase.白色链霉菌Gβ-内酰胺酶的活性位点丝氨酸突变体
Biochem J. 1991 Aug 1;277 ( Pt 3)(Pt 3):647-52. doi: 10.1042/bj2770647.
4
Engineering a novel beta-lactamase by a single point mutation.通过单点突变构建新型β-内酰胺酶。
Protein Eng. 1990 Oct;4(1):79-86. doi: 10.1093/protein/4.1.79.
5
Mechanism of acyl transfer by the class A serine beta-lactamase of Streptomyces albus G.白色链霉菌G的A类丝氨酸β-内酰胺酶的酰基转移机制
Biochem J. 1991 Oct 1;279 ( Pt 1)(Pt 1):213-21. doi: 10.1042/bj2790213.
6
Arginine 220 is a critical residue for the catalytic mechanism of the Streptomyces albus G beta-lactamase.
Protein Eng. 1991 Oct;4(7):811-9. doi: 10.1093/protein/4.7.811.
7
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.
8
Interactions between active-site serine beta-lactamases and so-called beta-lactamase-stable antibiotics. Kinetic and molecular modelling studies.
Eur J Biochem. 1993 Oct 1;217(1):61-7. doi: 10.1111/j.1432-1033.1993.tb18218.x.
9
Role of the conserved amino acids of the 'SDN' loop (Ser130, Asp131 and Asn132) in a class A beta-lactamase studied by site-directed mutagenesis.通过定点诱变研究“A类β-内酰胺酶中‘SDN’环（Ser130、Asp131和Asn132）保守氨基酸的作用”
Biochem J. 1990 Oct 15;271(2):399-406. doi: 10.1042/bj2710399.
10
Site-saturation mutagenesis and three-dimensional modelling of ROB-1 define a substrate binding role of Ser130 in class A beta-lactamases.ROB-1的位点饱和诱变和三维建模确定了A类β-内酰胺酶中Ser130的底物结合作用。
Protein Eng. 1992 Oct;5(7):693-701. doi: 10.1093/protein/5.7.693.
引用本文的文献
1
Machine Learning Classification Model for Functional Binding Modes of TEM-1 β-Lactamase.用于TEM-1β-内酰胺酶功能结合模式的机器学习分类模型
Front Mol Biosci. 2019 Jul 9;6:47. doi: 10.3389/fmolb.2019.00047. eCollection 2019.
2
Variations within class-A β-lactamase physiochemical properties reflect evolutionary and environmental patterns, but not antibiotic specificity.A 类β-内酰胺酶理化性质的差异反映了进化和环境模式，但不反映抗生素特异性。
PLoS Comput Biol. 2013;9(7):e1003155. doi: 10.1371/journal.pcbi.1003155. Epub 2013 Jul 18.
3
Mutagenesis of zinc ligand residue Cys221 reveals plasticity in the IMP-1 metallo-β-lactamase active site.锌配体残基 Cys221 的突变揭示了 IMP-1 金属β-内酰胺酶活性位点的可塑性。
Antimicrob Agents Chemother. 2012 Nov;56(11):5667-77. doi: 10.1128/AAC.01276-12. Epub 2012 Aug 20.
4
Structural basis of the inhibition of class A beta-lactamases and penicillin-binding proteins by 6-beta-iodopenicillanate.6-β-碘代青霉烷酸抑制 A 类β-内酰胺酶和青霉素结合蛋白的结构基础。
J Am Chem Soc. 2009 Oct 28;131(42):15262-9. doi: 10.1021/ja9051526.
5
Structural consequences of the inhibitor-resistant Ser130Gly substitution in TEM beta-lactamase.TEMβ-内酰胺酶中抑制剂抗性Ser130Gly替代的结构后果
Biochemistry. 2005 Jul 5;44(26):9330-8. doi: 10.1021/bi0502700.
6
Selection and characterization of beta-lactam-beta-lactamase inactivator-resistant mutants following PCR mutagenesis of the TEM-1 beta-lactamase gene.TEM-1β-内酰胺酶基因经PCR诱变后β-内酰胺-β-内酰胺酶灭活剂抗性突变体的筛选与鉴定
Antimicrob Agents Chemother. 1998 Jul;42(7):1542-8. doi: 10.1128/AAC.42.7.1542.
7
Catalytic properties of class A beta-lactamases: efficiency and diversity.A类β-内酰胺酶的催化特性：效率与多样性。
Biochem J. 1998 Mar 1;330 ( Pt 2)(Pt 2):581-98. doi: 10.1042/bj3300581.
8
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.
9
The mechanism of action of DD-peptidases: the role of Threonine-299 and -301 in the Streptomyces R61 DD-peptidase.D-丙氨酰-D-丙氨酸肽酶（DD-肽酶）的作用机制：苏氨酸-299和-301在链霉菌R61 DD-肽酶中的作用
Biochem J. 1994 Jul 15;301 ( Pt 2)(Pt 2):477-83. doi: 10.1042/bj3010477.
10
Families of serine peptidases.丝氨酸蛋白酶家族。
Methods Enzymol. 1994;244:19-61. doi: 10.1016/0076-6879(94)44004-2.
本文引用的文献
1
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.
2
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.
3
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.
4
Role of the conserved amino acids of the 'SDN' loop (Ser130, Asp131 and Asn132) in a class A beta-lactamase studied by site-directed mutagenesis.通过定点诱变研究“A类β-内酰胺酶中‘SDN’环（Ser130、Asp131和Asn132）保守氨基酸的作用”
Biochem J. 1990 Oct 15;271(2):399-406. doi: 10.1042/bj2710399.
5
A standard numbering scheme for the class A beta-lactamases.A类β-内酰胺酶的标准编号方案。
Biochem J. 1991 May 15;276 ( Pt 1)(Pt 1):269-70. doi: 10.1042/bj2760269.
6
Refined crystal structure of beta-lactamase from Staphylococcus aureus PC1 at 2.0 A resolution.
J Mol Biol. 1991 Feb 20;217(4):701-19. doi: 10.1016/0022-2836(91)90527-d.
7
Site-directed mutagenesis of beta-lactamase I. Single and double mutants of Glu-166 and Lys-73.β-内酰胺酶I的定点诱变。Glu-166和Lys-73的单突变体和双突变体。
Biochem J. 1990 Dec 15;272(3):613-9. doi: 10.1042/bj2720613.
8
Mechanism of acyl transfer by the class A serine beta-lactamase of Streptomyces albus G.白色链霉菌G的A类丝氨酸β-内酰胺酶的酰基转移机制
Biochem J. 1991 Oct 1;279 ( Pt 1)(Pt 1):213-21. doi: 10.1042/bj2790213.
9
Serine beta-lactamases and penicillin-binding proteins.丝氨酸β-内酰胺酶和青霉素结合蛋白。
Annu Rev Microbiol. 1991;45:37-67. doi: 10.1146/annurev.mi.45.100191.000345.
10
How specific is the effect of penicillins on the conformation of penicillinase? An experimental model.
Mol Pharmacol. 1979 Jul;16(1):250-5.
Zotero 插件