Carbapenemases are a large and diverse family of microbial enzymes that hydrolyze not only carbapenems but also other b-lactams, with the occasional exception of monobactams, such as aztreonam. For clinicians, the nomenclature of carbapenemases, like that of other b-lactamases, is confusing. In keeping with other b-lactamases, carbapenemases can be classified on the basis of function or structu...

Specific isoforms from the carbonic anhydrase (CA) family of zinc metalloenzymes have been associated with a variety of diseases. Isoform-specific carbonic anhydrase inhibitors (CAIs) are therefore a major focus of attention for specific disease treatments. Classical CAIs, primarily sulfonamide-based compounds and their bioisosteres, are examined as antiglaucoma, antiepileptic, antiobesity, ant...

The carbonic anhydrases (CAs) are mostly zinc-containing metalloenzymes which catalyze the reversible hydration/dehydration of carbon dioxide/bicarbonate. The CAs have been extensively studied because of their broad physiological importance in all kingdoms of life and clinical relevance as drug targets. In particular, human CA isoform II (HCA II) has a catalytic efficiency of 108 M-1 s-1, appro...

The alpha carbonic anhydrases (α-CAs) are a group of structurally related zinc metalloenzymes that catalyze the reversible hydration of CO2 to HCO3(-). Humans have 15 different α-CAs with numerous physiological roles and expression patterns. Of these, 12 are catalytically active, and abnormal expression and activities are linked with various diseases, including glaucoma and cancer. Hence there ...

Transition metal complexes are located at the active sites of a number of enzymes involved in intriguing biochemical reactions. These complexes can exhibit a wide variety of chemical reactivity due to the ease at which transition metals can adopt different coordination environments and oxidation states. Crystallography has been a powerful technique for examining the structure and conformational...

This paper summarizes recent research on the importance of zinc for human health, and reviews available methods of evaluating zinc status in individuals and populations. The lack of generally accepted biomarkers of zinc status has impeded estimation of the global prevalence of zinc deficiency. Although measurement of zinc consumption and/or plasma zinc concentration can be used to assess popula...

Bacterial α-carbonic anhydrases (α-CA) are zinc containing metalloenzymes that catalyze the rapid interconversion of CO2 to bicarbonate and a proton. We report the first crystal structure of a pyschrohalophilic α-CA from a deep-sea bacterium, Photobacterium profundum. Size exclusion chromatography of the purified P. profundum α-CA (PprCA) reveals that the protein is a heterogeneous mix of monom...

Streptococcus pneumoniae peptidoglycan GlcNAc deacetylase (SpPgdA) protects the Gram-positive bacterial cell wall from host lysozymes by deacetylating peptidoglycan GlcNAc residues. Deletion of the pgda gene has been shown to result in hypersensitivity to lysozyme and reduction of infectivity in a mouse model. SpPgdA is a member of the family 4 carbohydrate esterases, for which little structura...

conformational differences to the starting model, demonstrating the well-known need for allowing backbone flexibility in the design procedure. More information, however, would have been gained from a structure with bound substrate or transition state analog. Interestingly, both adenosine deaminase and the bacterial phosphotriesterase, which is known to hydrolyze organophosphate triesters with c...