Inhibitor binding primary structure

The primary, secondary, and presumably tertiary, and higher, structure of the family of facilitative glucose transporters are similar. It is beginning to be understood which domains of these transporters are important for substrate and inhibitor binding and for subcellular localization. Future work will undoubtably uncover the molecular mechanism by which the facilitative transporters catalyze the translocation of sugars across the membrane. 

In both bacteria and eucarya the susceptibility to certain ribosome-targeted inhibitors correlates with specific primary structural features of rR24A, or with features of the ribosomal domain that acts as the antibiotic binding sites. Firstly, resistance to specific ribosome-directed drugs is conferred by single-base changes within phylogenetically... 

Fig. 5.6. Secondary structure of the /3 subunit of E. coli F,. The primary structure of the protein was deduced from the DNA sequence [11]. The binding residues and numbers of binding sites for covalent inhibitors are also shown.

Primary structures of the Kunitz soybean trypsin inhibitor (A) and the Bowman-Birk soybean trypsin inhibitor (B). The solid black circles on the primary structure of the Bowman-Birk soybean trypsin inhibitor represent LYS-SER arid LEU-SER and are the binding sites far trypsin and chymotrypsin, respectively. Reproduced with permission from (A) Ref 73, copyright 1973, E. J. of Bioch. and (B) Ref 74, copyright 1973, J. Food Biochem.j... 

Further interpretation of the structure and its relation to the catalytic activity of this acid protease depends critically on the determination of the primary structure which is now being undertaken by Professor B. Foltmann and Dr. V. Pedersen. It also depends on the co-crystallization of the enzyme with active site-directed inhibitors unfortunately, we have been able to bind neither aromatic eposides nor pepstatin to the crystalline enzyme. 

Ribosomal Protein Synthesis Inhibitors. Figure 3 The chemical structure of tetracycline and possible interactions with 16S rRNA in the primary binding site. Arrows with numbers indicate distances (in A) between functional groups. There are no interactions obseived between the upper portion of the molecule and 16S rRNA consistent with data that these positions can be modified without affecting inhibitory action (from Brodersen et al. [4] with copynght permission). 

A virtual screen of 10,000 primary amine fragments against dipeptidyl peptidase IV (a diabetes target) identified a number of hits, as determined by bioassay screening at 100 pM, e.g. 6 [21]. An X-ray structure of this fragment confirmed the predicted binding mode in the Si pocket and inspired a structure-based hypothesis that eventually led to identification of a potent series of DPP-IV inhibitors [22],... 

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