Beta-lactamases are enzymes produced by bacteria that provide multi- resistance to β-lactam antibiotics such as penicillins, cephalosporins, cephamycins, and carbapenems (ertapenem), although carbapenems are relatively resistant to beta-lactamase. Beta-lactamase provides antibiotic resistance by breaking the antibiotics' structure. These antibiotics all have a common element in their molecular structure: a four-atom ring known as a β-lactam. Through hydrolysis, the enzyme lactamase breaks the β-lactam ring open, deactivating the molecule's antibacterial properties.
Hsp90 is a chaperone protein that assists other proteins to fold properly, stabilizes proteins against heat stress, and aids in protein degradation. It also stabilizes a number of proteins required for tumor growth, which is why Hsp90 inhibitors are investigated as anti-cancer drugs.
The beta hairpin is a simple protein structural motif involving two beta strands that look like a hairpin. The motif consists of two strands that are adjacent in primary structure, oriented in an antiparallel direction, and linked by a short loop of two to five amino acids. Beta hairpins can occur in isolation or as part of a series of hydrogen bonded strands that collectively comprise a beta sheet.
Anthrax toxin is a three-protein exotoxin secreted by virulent strains of the bacterium, Bacillus anthracis—the causative agent of anthrax. The toxin was first discovered by Harry Smith in 1954. Anthrax toxin is composed of a cell-binding protein, known as protective antigen (PA), and two enzyme components, called edema factor (EF) and lethal factor (LF). These three protein components act together to impart their physiological effects. Assembled complexes containing the toxin components are endocytosed. In the endosome, the enzymatic components of the toxin translocate into the cytoplasm of a target cell. Once in the cytosol, the enzymatic components of the toxin disrupts various immune cell functions, namely cellular signaling and cell migration. The toxin may even induce cell lysis, as is observed for macrophage cells. Anthrax toxin allows the bacteria to evade the immune system, proliferate, and ultimately kill the host animal. Research on anthrax toxin also provides insight into the generation of macromolecular assemblies, and on protein translocation, pore formation, endocytosis, and other biochemical processes.
A leucine-rich repeat (LRR) is a protein structural motif that forms an α/β horseshoe fold. It is composed of repeating 20–30 amino acid stretches that are unusually rich in the hydrophobic amino acid leucine. These tandem repeats commonly fold together to form a solenoid protein domain, termed leucine-rich repeat domain. Typically, each repeat unit has beta strand-turn-alpha helix structure, and the assembled domain, composed of many such repeats, has a horseshoe shape with an interior parallel beta sheet and an exterior array of helices. One face of the beta sheet and one side of the helix array are exposed to solvent and are therefore dominated by hydrophilic residues. The region between the helices and sheets is the protein's hydrophobic core and is tightly sterically packed with leucine residues.
Beta-lactamases are a family of enzymes involved in bacterial resistance to beta-lactam antibiotics. They act by breaking the beta-lactam ring that allows penicillin-like antibiotics to work. Strategies for combating this form of resistance have included the development of new beta-lactam antibiotics that are more resistant to cleavage and the development of the class of enzyme inhibitors called beta-lactamase inhibitors. Although β-lactamase inhibitors have little antibiotic activity of their own, they prevent bacterial degradation of beta-lactam antibiotics and thus extend the range of bacteria the drugs are effective against.
The EGF-like domain is an evolutionary conserved protein domain, which derives its name from the epidermal growth factor where it was first described. It comprises about 30 to 40 amino-acid residues and has been found in a large number of mostly animal proteins. Most occurrences of the EGF-like domain are found in the extracellular domain of membrane-bound proteins or in proteins known to be secreted. An exception to this is the prostaglandin-endoperoxide synthase. The EGF-like domain includes 6 cysteine residues which in the epidermal growth factor have been shown to form 3 disulfide bonds. The structures of 4-disulfide EGF-domains have been solved from the laminin and integrin proteins. The main structure of EGF-like domains is a two-stranded β-sheet followed by a loop to a short C-terminal, two-stranded β-sheet. These two β-sheets are usually denoted as the major (N-terminal) and minor (C-terminal) sheets. EGF-like domains frequently occur in numerous tandem copies in proteins: these repeats typically fold together to form a single, linear solenoid domain block as a functional unit.
Outer membrane receptors, also known as TonB-dependent receptors, are a family of beta barrel proteins named for their localization in the outer membrane of gram-negative bacteria. TonB complexes sense signals from the outside of bacterial cells and transmit them into the cytoplasm, leading to transcriptional activation of target genes. TonB-dependent receptors in gram-negative bacteria are associated with the uptake and transport of large substrates such as iron siderophore complexes and vitamin B12.
Vacuolar protein sorting-associated protein 26A is a protein that in humans is encoded by the VPS26A gene.
The inhibitor of apoptosis domain -- also known as IAP repeat, Baculovirus Inhibitor of apoptosis protein Repeat, or BIR -- is a structural motif found in proteins with roles in apoptosis, cytokine production, and chromosome segregation. Proteins containing BIR are known as inhibitor of apoptosis proteins (IAPs), or BIR-containing proteins, and include BIRC1 (NAIP), BIRC2 (cIAP1), BIRC3 (cIAP2), BIRC4 (xIAP), BIRC5 (survivin) and BIRC6.
The AT-hook is a DNA-binding motif present in many proteins, including the high mobility group (HMG) proteins, DNA-binding proteins from plants and hBRG1 protein, a central ATPase of the human switching/sucrose non-fermenting (SWI/SNF) remodeling complex.
In molecular biology, Phosphotyrosine-binding domains are protein domains which bind to phosphotyrosine.
In molecular biology, the CBS domain is a protein domain found in a range of proteins in all species from bacteria to humans. It was first identified as a conserved sequence region in 1997 and named after cystathionine beta synthase, one of the proteins it is found in. CBS domains are also found in a wide variety of other proteins such as inosine monophosphate dehydrogenase, voltage gated chloride channels and AMP-activated protein kinase (AMPK). CBS domains regulate the activity of associated enzymatic and transporter domains in response to binding molecules with adenosyl groups such as AMP and ATP, or s-adenosylmethionine.
Influenza non-structural protein (NS1) is a homodimeric RNA-binding protein found in influenza virus that is required for viral replication. NS1 binds polyA tails of mRNA keeping them in the nucleus. NS1 inhibits pre-mRNA splicing by tightly binding to a specific stem-bulge of U6 snRNA.
In molecular biology, the SAG1 protein domain is an example of a group of glycosylphosphatidylinositol (GPI)-linked proteins named SRSs. SAG1 is found on the surface of a protozoan parasite Toxoplasma gondii. This parasite infects almost any warm-blooded vertebrate. The surface of T. gondii is coated with a family of developmentally regulated glycosylphosphatidylinositol (GPI)-linked proteins (SRSs), of which SAG1 is the prototypic member.
In molecular biology, the protein domain SAND is named after a range of proteins in the protein family: Sp100, AIRE-1, NucP41/75, DEAF-1. It is localised in the cell nucleus and has an important function in chromatin-dependent transcriptional control. It is found solely in eukaryotes.
Tubulin/FtsZ family, GTPase domain is an evolutionary conserved protein domain.
Ubiquitin-associated (UBA) domains are protein domains that non-covalently interact with ubiquitin through protein-protein interactions. Ubiquitin is a small protein that is covalently linked to other proteins as part of intracellular signaling pathways, often as a signal for protein degradation. UBA domains are among the most common ubiquitin-binding domains.
In molecular biology, the Tymovirus coat protein refers to the protein coat of a virus order, named Tymovirales. More specifically this protein signature is found only in coat proteins from the related tymoviruses. The coat protein (CP) is also known as the virion protein. The virus coat is composed of 180 copies of the coat protein arranged in an icosahedral shell.
Natalie C. J. Strynadka FRS is a professor of Biochemistry in the Department of Biochemistry and Molecular Biology at the University of British Columbia.
