Lysine Biosynthesis in Bacteria: A Metallodesuccinylase as a Potential Antimicrobial Target

In this review, we summarize the recent literature on dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase (DapE) enzymes, with an emphasis on structure–function studies that provide insight into the catalytic mechanism. Crystallographic data have also provided insight into residues that might be involved in substrate and hence inhibitor recognition and binding. These data have led to the design and synthesis of several new DapE inhibitors, which are described along with what is known about how inhibitors interact with the active site of DapE enzymes, including the efficacy of a moderately strong DapE inhibitor

An Analytical Method for Detecting Toxic Metal Cations Using Cyclotriveratrylene Derivative Capped Gold Nanoparticles

Cyclotriveratrylene-oxime (CTV-oxime) derivatives that terminate with a dithiolate linker were synthesized enabling the supramolecular scaffold to adhere to gold nanoparticles (AuNPs) with the bowl-shaped cavity of the CTV scaffold exposed for utilization in host–guest chemistry. Exposure of these CTV functionalized AuNPs to varying concentrations of di- and trivalent metal cations resulted in the formation of large CTV-AuNP polymeric clusters and an accompanying a shift in the plasmon resonance. These interactions between the CTV-AuNPs and the metal cations in solution provides proof-of-concept that supramolecular functionalized AuNPs can be used as a simple and straightforward, on-site detection system for toxic metal cations in solution. The order of binding affinity of the metals studied based on observed Kd values is Cu2+ \u3e Zn2+ \u3e Pb2+ \u3e Hg2+ \u3e Eu3+ \u3e Cd2+

Inhibitors of Bacterial \u3cem\u3eN\u3c/em\u3e-succinyl-L,L-diaminopimelic Acid Desuccinylase (DapE) and Demonstration of in vitro Antimicrobial Activity

The dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE) is a critical bacterial enzyme for the construction of the bacterial cell wall. A screen biased toward compounds containing zinc-binding groups (ZBG’s) including thiols, carboxylic acids, boronic acids, phosphonates and hydroxamates has delivered a number of micromolar inhibitors of DapE from Haemophilus influenzae, including the low micromolar inhibitor L-captopril (IC50 = 3.3 μM, Ki = 1.8 μM). In vitro antimicrobial activity was demonstrated for l-captopril against Escherichia coli

Direct Patterning of a Cyclotriveratrylene Derivative for Directed Self-assembly of C60

A novel apex-modified cyclotriveratrylene (CTV) derivative with an attached thiolane-containing lipoic acid linker was directly patterned onto gold substrates via dip-pen nanolithography (DPN). The addition of a dithiolane-containing linker to the apex of CTV provides a molecule that can adhere to a gold surface with its bowl-shaped cavity directed away from the surface, thereby providing a surface-bound CTV host that can be used for the directed assembly of guest molecules. Subsequent exposure of these CTV microarrays to C60 in toluene resulted in the directed assembly of predesigned, spatially controlled, high-density microarrays of C60. The molecular recognition capabilities of this CTV template toward C60 provides proof-of-concept that supramolecular CTV scaffolds can be directly patterned onto surfaces providing a foundation for the development of organic electronic and optoelectronic materials

A Synopsis of the 1979 Amendments to the Federal Rules of Criminal Procedure

On April 30, 1979, the Supreme Court of the United States ordered the amendment of the Federal Rules of Criminal Procedure. The modifications ordered by the Court promise to bring about significant changes in the Rules, clarify ambiguous sections, eliminate confusion in application, and bring the Rules into conformity with recent case law. The process of amending the Federal Rules of Criminal Procedure began with the Advisory Committee on Criminal Rules of the Judicial Conference of the United States. The Advisory Committee was responsible for drafting the text of the proposed amendments and submitting explanatory comments. The proposed changes and additions were then sent to the Committee on Rules of Practice and Procedure of the Judicial Conference, which solicited comments from the bench and bar before submitting the amendments to the Judicial Conference. Subsequently, the Judicial Conference approved the proposed amendments and transmitted them to the Supreme Court. The Supreme Court then ordered these amendments to take effect on August 1, 1979. Upon receipt by Congress, the amendments to the Rules were referred to the House Subcommittee on Criminal Justice. Currently engaged in a major effort to overhaul the Federal Criminal Code, the Subcommittee was unable to study the proposed changes in detail. Consequently, the Subcommittee acted to delay the passage of those amendments that it regarded as particularly controversial or far-reaching. Accordingly, Congress delayed the effective dates of the modifications to rules 11(e)(6), 17(h), 32(f), and 44(c) and the enactment of rules 26.2 and 32.1 until a study of the changes could be made, or until December 1, 1980, whichever comes first. This comment will analyze the changes made in the Federal Rules, particularly noting the rationale for the various amendments and the intended effects of those changes

Lysine Biosynthesis in Bacteria: A Metallodesuccinylase as a Potential Antimicrobial Target

In this review, we summarize the recent literature on dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase (DapE) enzymes, with an emphasis on structure–function studies that provide insight into the catalytic mechanism. Crystallographic data have also provided insight into residues that might be involved in substrate and hence inhibitor recognition and binding. These data have led to the design and synthesis of several new DapE inhibitors, which are described along with what is known about how inhibitors interact with the active site of DapE enzymes, including the efficacy of a moderately strong DapE inhibitor

Red Sea Rifting Controls on Groundwater Reservoir Distribution: Constraints from Geophysical, Isotopic, and Remote Sensing Data

Highly productive wells in the Central Eastern Desert of Egypt are tapping groundwater in subsided blocks of Jurassic to Cretaceous sandstone (Taref Formation of the Nubian Sandstone Group) and Oligocene to Miocene sandstone (Nakheil Formation), now occurring beneath the Red Sea coastal plain and within the proximal basement complex. Aquifer development is related to Red Sea rifting: (1) rifting was accommodated by vertical extensional displacement on preexisting NW-SE– to N-S–trending faults forming a complex array of half-grabens and asymmetric horsts; and (2) subsided blocks escaped erosion accompanying the Red Sea–related uplift. Subsided blocks were identifi ed and verifi ed using satellite data, geologic maps, and fi eld and geophysical investigations. Interpretations of very low frequency (VLF) measurements suggest the faults acted as conduits for ascending groundwater from the subsided aquifers. Stable isotopic compositions (δD: –19.3‰ to –53.9‰; δ18O: –2.7‰ to –7.1‰) of groundwater samples from these aquifers are interpreted as mixtures of fossil (up to 70%) and modern (up to 65%) precipitation. Groundwater volumes in subsided blocks are large; within the Central Eastern Desert basement complex alone, they are estimated at 3 × 109 m3 and 10 × 109 m3 for the Nakheil and Taref Formations, respectively. Results highlight the potential for identifying similar rift-related aquifer systems along the Red Sea–Gulf of Suez system, and in rift systems elsewhere. An understanding of the distribution of Red Sea rift–related aquifers and modern recharge contributions to these aquifers could assist in addressing the rising demands for fresh water supplies and water scarcity issues in the regio

Red Sea Rifting Controls on Groundwater Reservoir Distribution: Constraints from Geophysical, Isotopic, and Remote Sensing Data

Highly productive wells in the Central Eastern Desert of Egypt are tapping groundwater in subsided blocks of Jurassic to Cretaceous sandstone (Taref Formation of the Nubian Sandstone Group) and Oligocene to Miocene sandstone (Nakheil Formation), now occurring beneath the Red Sea coastal plain and within the proximal basement complex. Aquifer development is related to Red Sea rifting: (1) rifting was accommodated by vertical extensional displacement on preexisting NW-SE– to N-S–trending faults forming a complex array of half-grabens and asymmetric horsts; and (2) subsided blocks escaped erosion accompanying the Red Sea–related uplift. Subsided blocks were identifi ed and verifi ed using satellite data, geologic maps, and fi eld and geophysical investigations. Interpretations of very low frequency (VLF) measurements suggest the faults acted as conduits for ascending groundwater from the subsided aquifers. Stable isotopic compositions (δD: –19.3‰ to –53.9‰; δ18O: –2.7‰ to –7.1‰) of groundwater samples from these aquifers are interpreted as mixtures of fossil (up to 70%) and modern (up to 65%) precipitation. Groundwater volumes in subsided blocks are large; within the Central Eastern Desert basement complex alone, they are estimated at 3 × 109 m3 and 10 × 109 m3 for the Nakheil and Taref Formations, respectively. Results highlight the potential for identifying similar rift-related aquifer systems along the Red Sea–Gulf of Suez system, and in rift systems elsewhere. An understanding of the distribution of Red Sea rift–related aquifers and modern recharge contributions to these aquifers could assist in addressing the rising demands for fresh water supplies and water scarcity issues in the regio