3D Protein Imaging’s Post

Lipopolysaccharide (LPS) is a major component of the outer leaflet of the outer membrane (OM) of Gram-negative bacteria. Lipid A functions as the hydrophobic membrane anchor of LPS and is linked via a core oligosaccharide to the long chain polysaccharide known as O-antigen. The lipid A-core portion (known as “rough” LPS (R-LPS)) is synthesized by a conserved pathway involving proteins on the cytoplasmic surface of the inner membrane (IM) and is then transported across the IM by an essential ATP-binding cassette (ABC) transporter, MsbA. Recently, five additional essential E. coli proteins (LptA, LptB, LptC (formerly YrbK), LptF (formerly YjgP), and LptG (formerly YjgQ)) have been implicated in LPS transport to the OM. LptA is a candidate for the chaperone delivering nascent LPS molecules to LptDE in the OM. Here you can see a recent crystal structure of the LptA protein from Escherichia coli (PDB code: 8GAJ) Rendering by Francisco J. Enguita made with #proteinimager https://lnkd.in/dzCVhWUe #molecularart #periplasm #gramnegative #cellwall #LptA #peptidoglycan #xray

Lysobisphosphatidic acids (LBPAs), known also as bis-(monoacylglycerol)phosphates (BMPs) are specialized lipids reported to play a role in intracellular protein and lipid transport in healthy cells.Accumulation of LBPAs in intracellular, often multilamellar membranes is related to biomembrane polymorphism which may impact intracellular cholesterol transport. (S,S) Bisoleoyl-lysobisphosphatidic acid is the naturally occurring, biologically active isomer of LPBA. #Lysobisphosphatidic #acids #LBPAs #intracellular #cholesterol #multilamellar https://lnkd.in/eZrDf6uA

From the abstract: In this study, we present a comprehensive peptidomimetic structure–activity relationship (SAR) approach, combined with cellular NanoBRET target engagement assays to enhance the existing VHL ligands. Through systematic modifications of the molecule, we identified the 1,2,3-triazole group as an optimal substitute of the left-hand side amide bond that yields 10-fold higher binding activity. Moreover, incorporating conformationally constrained alterations on the methylthiazole benzylamine moiety led to the development of highly potent VHL ligands with picomolar binding affinity and significantly improved oral bioavailability. We anticipate that our optimized VHL ligand, GNE7599, will serve as a valuable tool compound for investigating the VHL pathway and advancing the field of targeted protein degradation.

FMN transferase or Flavin Trafficking Protein is a primarily prokaryotic enzyme (also found in trypanosomatids) that covalently links FMN to threonine residues of periplasmic enzymes critical for existence of many bugs, including Salmonella, Syphilis (a "Flavin Specialist") and Gonorrhea. I have determined the structure of this enzyme bound to Adenine (below). In-crystallo cleavage of FAD to Adenine within yellow crystals results in new clear crystals with secondary and tertiary conformational rearrangements, expelling all sulfates and resulting in an asymmetric dimer structure with a novel putative active site. The FAD appears to act as a small-molecule "Chaperone" to assist in proper folding to an as yet unknown functional state.

How Proteins cleaved with Cyanogen bromide Cyanogen bromide is often used to immobilize proteins by coupling them to reagents such as agarose for affinity chromatography. Because of its simplicity and mild pH conditions, cyanogen bromide activation is the most common method for preparing affinity gels. Cyanogen bromide is also often used because it reacts with the hydroxyl groups on agarose to form cyanate esters and imidocarbonates. These groups are reacted with primary amines in order to couple the protein onto the agarose matrix, as shown in the figure. Because cyanate esters are more reactive than are cyclic imidocarbonates, the amine will react mostly with the ester, yielding isourea derivatives, and partially with the less reactive imidocarbonate, yielding substituted imidocarbonates. The disadvantages of this approach include the toxicity of cyanogen bromide and its sensitivity to oxidation. Also, cyanogen bromide activation involves the attachment of a ligand to agarose by an isourea bond, which is positively charged at neutral pH and thus unstable. Consequently, isourea derivatives may act as weak anion exchangers. Cyanogen bromide hydrolyzes peptide bonds at the C-terminus of methionine residues. This reaction is used to reduce the size of polypeptide segments for identification and sequencing. Youtube video: https://lnkd.in/dNfv2QXR #nikolaysgeneticslessons

Learn about the Specificity of our Fluorescent Protein Nanoantibodies! Did you know that due to the structural similarity of many fluorescent proteins (FPs), a single nanoantibody (nAb™) can recognize several FPs, despite being initially intended to bind a specific one? In the link below you'll find the FPs that Allele’s nAbs recognize, which include nAbs against GFP, mTFP, RFP, and mNeonGreen! https://lnkd.in/gGx2iprJ

SOURCE AND CHEMISTRY OF CARDIAC GLYCOSIDES :: Cardiac glycosides digitoxin gitoxin and gilatin are obtained from the leaves of Digitalis purpurea Digoxin and Ouabain are obtained from D lanata leaves and Strophanthus gratus seeds respectively Each glycoside is a combination of an aglycone or genin with one to four molecules of sugar The pharmacological activity resides in aglycone but the particular sugars attached to aglycone modify water solubility cell permeability and potency of the resulting glycosides  https://lnkd.in/d-2WjnND

Further development of adenosine receptor positive allosteric modulators in collaboration with the Jacobson lab at the NIH and introduction of the concept of 'lipid trolling' to optimize molecular interactions with a lipid-exposed transmembrane protein binding site. https://lnkd.in/gmse4VPZ