Crystal structures of the cadmium- and mercury-substituted metallo-beta-lactamase from Bacteroides fragilis

Protein Science : a Publication of the Protein Society
N O ConchaO Herzberg

Abstract

The metallo-beta-lactamases require zinc or cadmium for hydrolyzing beta-lactam antibiotics and are inhibited by mercurial compounds. To data, there are no clinically useful inhibitors of this class of enzymes. The crystal structure of the Zn(2+)-bound enzyme from Bacteroides fragilis contains a binuclear zinc center in the active site. A hydroxide, coordinated to both zinc atoms, is proposed as the moiety that mounts the nucleophilic attack on the carbonyl carbon atom of the beta-lactam ring. To study the metal coordination further, the crystal structures of a Cd(2+)-bound enzyme and of an Hg(2+)-soaked zinc-containing enzyme have been determined at 2.1 A and 2.7 A, respectively. Given the diffraction resolution, the Cd(2+)-bound enzyme exhibits the same active-site architecture as that of the Zn(2+)-bound enzyme, consistent with the fact that both forms are enzymatically active. The 10-fold reduction in activity of the Cd(2+)-bound molecule compared with the Zn(2+)-bound enzyme is attributed to fine differences in the charge distribution due to the difference in the ionic radii of the two metals. In contrast, in the Hg(2+)-bound structure, one of the zinc ions, Zn2, was ejected, and the other zinc ion, Zn1, remained in the sa...Continue Reading

References

Nov 1, 1978·The Biochemical Journal·G S BaldwinE P Abraham
Oct 1, 1974·The Biochemical Journal·R B Davies, E P Abraham
Jan 1, 1966·The Biochemical Journal·L D Sabath, E P Abraham
Aug 1, 1993·Journal of Medical Microbiology·D J Payne
Apr 1, 1993·Antimicrobial Agents and Chemotherapy·K BushY Yang
Jan 1, 1997·Antimicrobial Agents and Chemotherapy·D J PayneJ Marchand-Brynaert

❮ Previous
Next ❯

Citations

Mar 16, 2001·Bioorganic & Medicinal Chemistry·S BounagaM I Page
Oct 6, 1999·Current Opinion in Chemical Biology·Z WangS J Benkovic
Mar 6, 1999·Current Opinion in Microbiology·K Bush, G H Miller
May 2, 2003·Proceedings of the National Academy of Sciences of the United States of America·Xavier BaillyDidier Jollivet
Apr 21, 1999·Protein Science : a Publication of the Protein Society·Z LiO Herzberg
Jun 14, 2008·Bioinorganic Chemistry and Applications·Michael I Page, Adriana Badarau
Apr 4, 2014·Metallomics : Integrated Biometal Science·A I KarsisiotisG C K Roberts
May 2, 2008·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Adriana Badarau, Michael I Page
May 9, 2014·Metallomics : Integrated Biometal Science·Lu TangShizhong Wang
Jul 1, 2020·Journal of Medical Microbiology·Kerry Yang, Yanjie Zhang
Oct 15, 2019·Frontiers in Genetics·Dixit SharmaShailender Kumar Verma
Jun 8, 2001·The Journal of Biological Chemistry·J H ToneyY D Gao
Mar 10, 2001·Angewandte Chemie·Henry Strasdeit
Jul 17, 1998·Current Opinion in Chemical Biology·J E Coleman
Jun 13, 2006·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·Christine ChabasseFranck Zal
Oct 18, 2001·Journal of the American Chemical Society·L HemmingsenR Bauer

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.