Assignment ( Hatters ) ( Transthyretin )

3. The subject who was diagnosed with hyperthyroidism was given propylthiouracil (prevents Thyroxine production and conversion

sHSPs are a ubiquitous class of chaperones found across all kingdoms of life. sHSP range in size from 12-42 kilo Daltons in large oligomers of 12 to >32 subunits and the structure is homologous across all species. The sHSP monomer consists of three domains: a disordered N-terminal arm, a beta-sandwich α-crystallin domain, and a flexible C-terminal extension. The N-terminal domain is the most variable region with little conservation between species. Experimental evidence also suggests N-terminal involvement in substrate binding and protection. The α-crystallin domain is the most highly conserved region and adopts a β-sandwich conformation composed of 7 to 8 anti-parallel β-strands (Basha et al, 2012). The C-terminus contains an I-X-I motif, which helps to satblizie the oligomeric form of the sHSP (Basha et al, 2012).

Figure 1.b shows the ‘Lock and Key’ model where two individual substrates meet the active site where

-terminal fragment of the YFP was fused to the N-terminus of TuHC and AtCA1 to make YFPN-TuHC and YFPN-AtCA1, respectively, while the C-terminal fragment of the YFP was fused to the N-terminus of TuHC and TuMV CP (TuCP)

To characterise the target engagement of MP-10, Schülke et al. designed a photoaffinity probe for PDE10A which contained a linker attached to the PDE10A recognition element (Figure 4), so that a reporter group could be introduced without effecting the proteins activity. The group decided, via studying the cocrystal structure, that the pyrazole nitrogen would be the best site for linker attachment as it is unsubstituted and a relatively synthetically accessible point of modification. Adding to

Figure 1 Structure of G-protein-coupled receptor, showing alpha-helical proteins attached to the three subunits of the G-protein.

FS activates the AC isoforms by binding in between the C1 and C2 domains and interacting with residues there with a combination of hydrophobic interactions and hydrogen bonding. These interactions are largely equally

Enhance the affinity of the recognition site for GABA by inducing conformational changes that make GABA binding more efficacious.

Alpha and beat beta chains fold up together to form similar three-dimensional structures, they held together by non-covalent interactions. Each chain contain a one unit of heme which have a four binding sites for oxygen ().

Looking at Figure 3, the crystal structure of FFA1 provides a good starting point for understanding ligand docking which predicts the preferred orientation of one molecule to a second molecule when bound to each other to form a stable complex. Although docking of flexible Linoleic acid which is a natural ligand is the least reliable, it helps to generate hypotheses as to how agonistic activity of Linoleic acid could be amplified by synthetic agonists, like TAK-875, at a structural level. For example, targeting Arginines, which are α-amino acids that are used in the biosynthesis of proteins, from the extracellular side by substituting existing water-mediated contacts could still leave a possibility of targeting the Arginines from the side involved in interactions with amino acids Tyrosines. The fact that the ligands could have different binding modes and occupy different binding sites at FFA1 can be also seen from a site map search (Schrodinger, LLC, New York, NY, USA 2014b) (Fig. 3, E)11.

Tachylectin-5A is an ellipsoidal molecule that is an asymmetrical monomer, which is subdivided into three different domains that interact with each other (2). The primary structure of Tachylectin-5A constitutes 269 amino acid residues (1). The amino acid composition of this protein has a cis-peptide bone between Arg-218 and Cys-219 (3). It contains one protein modification called prryolidone carboxylic acid, which is the twenty-fourth amino acid in the sequence (1). And the secondary structure of the protein consists of 16% alpha helical and 24% beta sheets. There are 9 helices with 44 amino acid residues and 19 beta sheets with 66 residues involved in total (1). The

The enzyme glutaminase resides inside the mitochondria as a homodimer, in which state it is inactive. Once it gets activated, two dimers combine to form the catalytically active homotetramer. (2) The interface between the two dimers consists of two symmetrical alpha helices that interact by stacking between the residues Asp391 and Lys401. The tetramerization causes the gating loop to open and allows the substrate glutamine to bind.

Any other heme proteins and other metalloenzymes are inhibited by the sodium azide. Azide also inhibits the ATP hydrolase activity of the mitochondrial F-ATPase but not its synthetic activity. The F-ATPase in the eubacteria and the chloroplast share similar effect as the azide. The azide ions interact the β-phosphate of ADP with the residue of the ADP-binding catalytic subunit, βDP, thus occupying the position between the catalytically essential amino acids, β-Lys-162 in the P loop and the “arginine finger” residue, α-Arg-373. This is similar to the y phosphate occupying the ATP-binding subunit, βTP. The βTP substance appears to tighten the side of the nucleotide, enhancing its affinity and thereby stabilizing the state with bound ADP. The similar functions share F-ATPase embeds the inner membrane of the mitochondria. Sodium Azide inhibits ATP hydrolysis by binding F1 catalytic domain, assembling three α- and three β-subunits. The membrane-bound sector contains a central stalk and a peripheral stalk appears to be alter as the sodium azide inhibits. During ATP hydrolysis, the F1-ATPase is trapped in a catalytic state because either the ADP has fail to release enzyme during the ATP hydrolysis, or the ADP is bound from the medium. This has a major effect on the ADP·Mg2+, heavily affected by sodium azide. The sodium azide blocks the catalytic sites to inactivate the ATP

The primary protein structure can be likened to a human chain in which each person is assumed to be an amino acid and their hands viewed as the carboxyl and amino groups. The person on one end of the chain, who has a free left hand, is assumed to be the free carboxyl group. The person on the other end, who has a free right hand, is assumed to be the free amino group. Everyone in this chain has a left hand linked to somebody’s right hand and a right hand linked to somebody else’s left hand forming peptide bonds. The heads and legs just like the side chains and hydrogens, do not take part in the linking.

For the presence of substrates or inhibitors, the zinc active site has several characters for the substrates binding and activation. Firstly, carboxylate group of the Glu-72 becomes coordinated in a more nearly monodentate way. Secondly, there is a hydrophobic pocket near the active site where the aromatic ring in the C-terminal end of the substrate molecule can reside into the pocket help cleave the terminal peptide bond. In addition, the coordinated water molecule can form hydrogen bond with Glu-270 beside the active site. Also several Arg and Tyr residues are positioned in the active site allowing them to participate in substrate binding and activation.