New Delhi metallo-β-lactamase (NDM-1) has created a medical storm ever since it was first reported;as it is active on virtually all clinically used β-lactam antibiotics. NDM-1 rampancy worldwide is now considered a ...New Delhi metallo-β-lactamase (NDM-1) has created a medical storm ever since it was first reported;as it is active on virtually all clinically used β-lactam antibiotics. NDM-1 rampancy worldwide is now considered a nightmare scenario, particularly due to its rapid dissemination. An underlying theme in the majority of recent studies is structural characterization as knowledge of the three-dimensional structure of NDM-1 shall help find connections between its structure and function. Moreover, structural details are even critical in order to reveal the resistance mecha- nism to β-lactam antibiotics. In this perspective, we review structural characteristics of NDM-1 that have been delineated since its first report. We anticipate that these structure-function connections made by its characterization shall further serve as future guidelines for elucidating pathways towards de novo design of functional inhibitors.展开更多
Aliphatic homo-polypeptoids of NAla, NVal, NIle and NLeu both in the presence and absence of protecting groups adopt helical structures without hydrogen bonds with Φ, Ψ values of ~ 0, ± 90° with trans amid...Aliphatic homo-polypeptoids of NAla, NVal, NIle and NLeu both in the presence and absence of protecting groups adopt helical structures without hydrogen bonds with Φ, Ψ values of ~ 0, ± 90° with trans amide bonds. These structures are stabilized by carbonyl-carbonyl interactions and characterized by ~ 3.16 residues per turn with a pitch of ~ 6.13 ?. It has been shown that like polyvaline and polyleucine peptides, poly-peptoids can also be exploited for the construction of potential surfactant like molecules by incorporating charged amino acid residues at the N terminal. A single-handed template with Φ, Ψ values of ~ 0, 90° can be attained by incorporating L-leu or L-val at the C-terminal of poly-NIle. Analysis of the simulation results in water as a function of time reveals that the opening of helical structures without hydrogen bonds takes place at sub-picosecond time scale starting from the N-terminal. This leads to the formation of collagen or inverse-collagen type structures (Φ, Ψ ~ -60, 145° and 60, -145° respectively) stabilized by interactions of water molecules with the backbone carbonyl groups.展开更多
文摘New Delhi metallo-β-lactamase (NDM-1) has created a medical storm ever since it was first reported;as it is active on virtually all clinically used β-lactam antibiotics. NDM-1 rampancy worldwide is now considered a nightmare scenario, particularly due to its rapid dissemination. An underlying theme in the majority of recent studies is structural characterization as knowledge of the three-dimensional structure of NDM-1 shall help find connections between its structure and function. Moreover, structural details are even critical in order to reveal the resistance mecha- nism to β-lactam antibiotics. In this perspective, we review structural characteristics of NDM-1 that have been delineated since its first report. We anticipate that these structure-function connections made by its characterization shall further serve as future guidelines for elucidating pathways towards de novo design of functional inhibitors.
文摘Aliphatic homo-polypeptoids of NAla, NVal, NIle and NLeu both in the presence and absence of protecting groups adopt helical structures without hydrogen bonds with Φ, Ψ values of ~ 0, ± 90° with trans amide bonds. These structures are stabilized by carbonyl-carbonyl interactions and characterized by ~ 3.16 residues per turn with a pitch of ~ 6.13 ?. It has been shown that like polyvaline and polyleucine peptides, poly-peptoids can also be exploited for the construction of potential surfactant like molecules by incorporating charged amino acid residues at the N terminal. A single-handed template with Φ, Ψ values of ~ 0, 90° can be attained by incorporating L-leu or L-val at the C-terminal of poly-NIle. Analysis of the simulation results in water as a function of time reveals that the opening of helical structures without hydrogen bonds takes place at sub-picosecond time scale starting from the N-terminal. This leads to the formation of collagen or inverse-collagen type structures (Φ, Ψ ~ -60, 145° and 60, -145° respectively) stabilized by interactions of water molecules with the backbone carbonyl groups.
