Pepsin: Difference between revisions

Pepsin is bilobal, and composed of two nearly equal N and C domains related by an intra dyad <ref name="flexible" />. There are 326 residues in pepsin, forming two topologically similar lobes. Residues 1-175 form the N-terminal lobe, and residues 176-327 constitute the C-terminal lobe. A large portion of the residues are polar and buried <ref name="Xray" />. Each of these domains consists predominantly of β-sheets <ref name="flexible" />. In fact, 44% of the structures residues are within a β-sheet. There are six small right-handed α-helical segments, the longest being hc which spans from residues 225-236. All the a-helices except h'c are partially exposed and have some amphiphilic characteristics especially hc. Hc has a solvated surface and a buried side <ref name="Xray" />. The two most prominent strands of mixed β-sheets in both domains are 1N and 1C sheets. These sheets are related by an intra-lobe topological 2-fold symmetry. The most important β-sheet consists of six anti-parallel β-strands. “Two further β-sheets, 2N and 2C are each related by an intra-lobe topologically related β-hairpins, folded below the 1N and 1C sheets. Further, a six-stranded sheet spans the two lobes and forms a structure resembling an arch upon which the other four strands reside <ref name="Xray" />.” The overall peptide folds and active site structures are homologous <ref name="flexible" />. Aspartic proteinases, including pepsin are distinguishable by the presence of two conserved aspartic acid residues in the active site <ref name="flexible" />. Each domain in pepsin contains one of two catalytically important aspartic acid residues <ref name="flexible" />. The interface between sheets 1N and 1C forms the catalytic center consisting of the two nearly co-planar carboxyl groups of aspartate residues <scene name='Sandbox_179/Asp/1'>32 and 215</scene>, that are held in close proximity by a network of hydrogen bonds, and are shielded from solvents by a β-hairpin loop. Both catalytic residues can be protonated, although only one carboxyl group can be negatively charged at any one time <ref name="Xray" />.  The side chains are involved in hydrogen-bond interactions with the main chain of the protein or other conserved side-chains of the enzyme <ref name="Xray" />.”  Hydrogen-bonds are what stabilize the fold of pepsin. This stabilization is called the fireman`s grip. About 188 main-chain-main –chain hydrogen bonds exist. The enzyme also has a high proportion of serine and threonine residues, the total being 60. Of these, 32 are involved with side-chain hydrogen-bond interactions with other residues of the enzyme. There are 2425 non-hydrogen protein atoms and 371 water molecules <ref name="Xray" /> . Pepsin has a very low pI in the range of 2-3 pH units, which is due to the high proportion of carboxyl residues, there is a total of 43. The protein is phosphorylated at Ser68 and has three disulphide bridges. Furthermore, pepsin contains several salt-bridges. One salt-bridge connecting the molecules at the 206 to 210 positions enclose the pepsins only type II turn. Type I turns are the most prevalent in pepsin <ref name="Xray" />. Lastly, are typically three basic residues in pepsin, Arg308, His53, and Lys320.   

<scene name='Pepsin/Pepsin/1'>active site aspartates</scene>  

<scene name='Pepsin/Disulfide/1'>three disulfide bridges</scene>