2PSG

REFINED STRUCTURE OF PORCINE PEPSINOGEN AT 1.8 ANGSTROMS RESOLUTION

Summary for 2PSG

• Entry DOI: 10.2210/pdb2psg/pdb
• Descriptor: PEPSINOGEN (2 entities in total)
• Functional Keywords: hydrolase(acid proteinase zymogen)
• Biological source: Sus scrofa (pig)
• Cellular location: Secreted: P00791
• Total number of polymer chains: 1
• Total formula weight: 39631.50

Authors

James, M.N.G.,Sielecki, A.R. (deposition date: 1991-01-23, release date: 1992-10-15, Last modification date: 2024-10-16)

Primary citation

Sielecki, A.R.,Fujinaga, M.,Read, R.J.,James, M.N.
Refined structure of porcine pepsinogen at 1.8 A resolution.
J.Mol.Biol., 219:671-692, 1991

PubMed Abstract: 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.

PubMed: 2056534
DOI: 10.1016/0022-2836(91)90664-R

Experimental method

X-RAY DIFFRACTION (1.8 Å)