2psg
From Proteopedia
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REFINED STRUCTURE OF PORCINE PEPSINOGEN AT 1.8 ANGSTROMS RESOLUTION
Overview
The molecular structure of porcine pepsinogen at 1.8 A resolution has been, determined by a combination of molecular replacement and multiple, isomorphous phasing techniques. The resulting structure was refined by, restrained-parameter least-squares methods. The final R factor [formula:, see text] is 0.164 for 32,264 reflections with I greater than or equal to, sigma (I) in the resolution range of 8.0 to 1.8 A. The model consists of, 2785 protein atoms in 370 residues, a phosphoryl group on Ser68 and 238, ordered water molecules. The resulting molecular stereochemistry is, consistent with a well-refined crystal structure with co-ordinate accuracy, in the range of 0.10 to 0.15 A for the well-ordered regions of the, molecule (B less than 15 A2). For the enzyme portion of the zymogen, the, root-mean-square difference in C alpha atom co-ordinates with the refined, porcine pepsin structure is 0.90 A (284 common atoms) and with the C alpha, atoms of penicillopepsin it is 1.63 A (275 common atoms). The additional, 44 N-terminal amino acids of the prosegment (Leu1p to Leu44p, using the, letter p after the residue number to distinguish the residues of the, prosegment) adopt a relatively compact structure consisting of a long, beta-strand followed by two approximately orthogonal alpha-helices and a, short 3(10)-helix. Intimate contacts, both electrostatic and hydrophobic, interactions, are made with residues in the pepsin active site. The, N-terminal beta-strand, Leu1p to Leu6p, forms part of the six-stranded, beta-sheet common to the aspartic proteinases. In the zymogen the first 13, residues of pepsin, Ile1 to Glu13, adopt a completely different, conformation from that of the mature enzyme. The C alpha atom of Ile1 must, move approximately 44 A in going from its position in the inactive zymogen, to its observed position in active pepsin. Electrostatic interactions of, Lys36pN and hydrogen-bonding interactions of Tyr37pOH, and Tyr90H with the, two catalytic aspartate groups, Asp32 and Asp215, prevent substrate access, to the active site of the zymogen. We have made a detailed comparison of, the mammalian pepsinogen fold with the fungal aspartic proteinase fold of, penicillopepsin, used for the molecular replacement solution. A, structurally derived alignment of the two sequences is presented.
About this Structure
2PSG is a Single protein structure of sequence from [1] with PO3 as ligand. Full crystallographic information is available from OCA.
Reference
Refined structure of porcine pepsinogen at 1.8 A resolution., Sielecki AR, Fujinaga M, Read RJ, James MN, J Mol Biol. 1991 Jun 20;219(4):671-92. PMID:2056534
Page seeded by OCA on Wed Nov 21 13:39:05 2007
