NDM-1, the ultimate promiscuous enzyme: substrate recognition and catalytic mechanism.

The specter of a return to an era in which infectious disease looms as a significant threat to human health is not just hyperbole; there are serious concerns about the widespread overuse and misuse of antibiotics contributing to increased antibiotic resistance in pathogens. The recent discovery of a new enzyme, first identified in Klebsiella pneumoniae from a patient from New Delhi and denoted as NDM-1, represents an example of extreme promiscuity: It hydrolyzes and inactivates nearly all known β-lactam-based antibiotics with startling efficiency. NDM-1 can utilize different metal cofactors and seems to exploit an alternative mechanism based on the reaction conditions.

Characterization of member of DUF1888 protein family, self-cleaving and self-assembling endopeptidase.

The crystal structure of SO1698 protein from Shewanella oneidensis was determined by a SAD method and refined to 1.57 Å. The structure is a β sandwich that unexpectedly consists of two polypeptides; the N-terminal fragment includes residues 1-116, and the C-terminal one includes residues 117-125.

Dynamical probing of allosteric control in nuclear receptors.

The dynamical behavior of the nuclear receptor LXR/RXR heterodimer was investigated with molecular dynamics simulations. The simulations reveal correlated motion between residues across the dimer interface that depends significantly on occupation of the ligand binding sites of the monomers. These results are broadly consistent with the observed experimental behavior of the dimers, where structural perturbation is thought to be a key element in signal transduction.

High-resolution structure of the nitrile reductase QueF combined with molecular simulations provide insight into enzyme mechanism.

Here, we report the 1.53-Å crystal structure of the enzyme 7-cyano-7-deazaguanine reductase (QueF) from Vibrio cholerae, which is responsible for the complete reduction of a nitrile (CN) bond to a primary amine (H(2)C-NH(2)). At present, this is the only example of a biological pathway that includes reduction of a nitrile bond, establishing QueF as particularly noteworthy.

Cervical spinal cord injury and the need for cardiovascular intervention.

Hypothesis: The level of cervical spinal cord injury (CSCI) can be used to predict the need for a cardiovascular intervention.

Design: Retrospective review. Data included level of spinal cord injury, Injury Severity Score, lowest heart rate, and systolic blood pressure in the first 24 hours and intensive care unit course.