Sandbox 179: Difference between revisions

Pepsin is bilobal, composed of two nearly equal N and C domains related by an intra dyad <ref name="flexible" />. Each of these domains consists predominantly of β-sheets <ref name="flexible" />. 44% of the structures residues are within a β-sheet, although there are six small right-handed α-helical segments, the longest being hc which spans from residues 225-236. All of the a-helices except h`c are partially exposed and have some amphiphilic character especially hc, which has a solvated surface and a buried side <ref name="Xray" />. The two most prominent strands of mixed β-sheets are 1N and 1C, these sheets are related by an intra-lobe topological 2-fold symmetry. The most important β-sheet consists of six anti-parallel β-strands, this sheet is called sheet 3. “Two further β-sheets, 2N and 2C are each related by an intra-lode 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 interface between sheets 1N and 1C forms the catalytic center consisting of the nearly co-planar carboxyl group of aspartate residues <scene name='Sandbox_179/Asp/1'>32 and 215</scene>, which are held in close proximity by a network of hydrogen bonds, and which are shielded from solvents by a β-hairpin loop. Both catalytic residues may be protonated, although only one carboxyl group would be negatively charged at any one time <ref name="Xray" />. The overall peptide folds and active sites 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" />. 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" />. 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 stabilizing 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, 43. The protein is phosphorylated at Ser68 and has three disulphide bridges. Pepsin also contains several salt-bridges one of which from 206 to 210 encloses the pepsins only type II turn. Type I turns are the most prevalent in pepsin <ref name="Xray" />. There are typically three basic residues in pepsin, Arg308, His53, and Lys320.