体诱导的质子转移和低屏障键由X射线晶体学揭示
Derek A Nichols1, Jacqueline C Hargis2, Ruslan Sanishvili3
1†Department of Molecular Medicine, University of South Florida College of Medicine, 12901 Bruce B. Downs Blvd, MDC 3522, Tampa, Florida 33612, United States.
Journal of the American Chemical Society
|June 10, 2015
概括
联体结合通过诱导质子转移和在CTX-Mβ-lactamase内形成低屏障键 (LBHBs) 来改变酶催化. 这些结构揭示了LBHBs.
科学领域:
- 酶学和结构生物学 酶学和结构生物学
- 生物物理化学 生物物理化学
背景情况:
- 带结合可以调节蛋白质残留的pKa值,影响酶催化.
- 了解质子化状态对于阐明酶机制至关重要.
研究的目的:
- 使用超高分辨率X射线晶体学可视化CTX-Mβ-乳酸酶酶途径期间的质子化状态变化.
- 调查连接体结合在形成低屏障键 (LBHBs) 的作用及其对催化作用的影响.
主要方法:
- 超高分辨率 (0.790.84 Å) CTX-M β-乳酸酶的X射线晶体结构.
- 对阿波,先等价和化过渡状态模拟复合物的分析.
- 量子力学/分子力学 (QM/MM) 反应路径计算.
主要成果:
- 在结时从Ser70转移到Glu166的质子转移的直接可视化.
- 在前价复合体中,在Ser70和Lys73之间观察2.53 Å的低屏障键 (LBHB).
- QM/MM计算显示了较低的质子转移障碍 (1.53 kcal/mol),并表明LBHBs稳定了过渡状态.
结论:
- 灵诱导的溶解产生了一个微环境,有利于在酶活性位点形成LBHB.
- 在一般的酸催化中,LBHBs可能有助于过渡状态稳定.
- 对于精确的蛋白质 - 配体相互作用建模,残留质子化状态的变化至关重要.
相关概念视频
Ligand Binding Sites
15.9K
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
15.9K
Hydrogen Bonds
16.4K
A hydrogen bond is formed when a weakly positive hydrogen atom already bonded to one electronegative atom (for example, the oxygen in the water molecule) is attracted to another electronegative atom from another polar molecule, such as water (H2O), hydrogen fluoride (HF), or ammonia (NH3). The huge electronegativity difference between the H atom (2.1) and the atom to which it is bonded (4.0 for an F atom, 3.5 for an O atom, or 3.0 for an N atom), combined with the very small size of an H atom...
16.4K
Hydrogen Bonds
136.5K
Hydrogen bonds are weak attractions between atoms that have formed other chemical bonds. One of these atoms is electronegative, like oxygen, and has a partial negative charge. The other is a hydrogen atom that has bonded with another electronegative atom and has a partial positive charge.
Hydrogen Bonds Control the World!
Because hydrogen has very weak electronegativity when it binds with a strongly electronegative atom, such as oxygen or nitrogen, electrons in the bond are unequally shared....
Hydrogen Bonds Control the World!
Because hydrogen has very weak electronegativity when it binds with a strongly electronegative atom, such as oxygen or nitrogen, electrons in the bond are unequally shared....
136.5K
Crystal Field Theory - Octahedral Complexes
32.0K
Crystal Field Theory
To explain the observed behavior of transition metal complexes (such as colors), a model involving electrostatic interactions between the electrons from the ligands and the electrons in the unhybridized d orbitals of the central metal atom has been developed. This electrostatic model is crystal field theory (CFT). It helps to understand, interpret, and predict the colors, magnetic behavior, and some structures of coordination compounds of transition metals.
CFT focuses on...
To explain the observed behavior of transition metal complexes (such as colors), a model involving electrostatic interactions between the electrons from the ligands and the electrons in the unhybridized d orbitals of the central metal atom has been developed. This electrostatic model is crystal field theory (CFT). It helps to understand, interpret, and predict the colors, magnetic behavior, and some structures of coordination compounds of transition metals.
CFT focuses on...
32.0K
Metal-Ligand Bonds
25.7K
The hemoglobin in the blood, the chlorophyll in green plants, vitamin B-12, and the catalyst used in the manufacture of polyethylene all contain coordination compounds. Ions of the metals, especially the transition metals, are likely to form complexes.
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
25.7K
Noncovalent Attractions in Biomolecules
66.1K
Noncovalent attractions are associations within and between molecules that influence the shape and structural stability of complexes. These interactions differ from covalent bonding in that they do not involve sharing of electrons.
Four types of noncovalent interactions are hydrogen bonds, van der Waals forces, ionic bonds, and hydrophobic interactions.
Hydrogen bonding results from the electrostatic attraction of a hydrogen atom covalently bonded to a strong-electronegative atom like oxygen,...
Four types of noncovalent interactions are hydrogen bonds, van der Waals forces, ionic bonds, and hydrophobic interactions.
Hydrogen bonding results from the electrostatic attraction of a hydrogen atom covalently bonded to a strong-electronegative atom like oxygen,...
66.1K


