3HGP

Structure of porcine pancreatic elastase complexed with a potent peptidyl inhibitor FR130180 determined by high resolution crystallography

Summary for 3HGP

• Entry DOI: 10.2210/pdb3hgp/pdb
• Related: 3HGN
• Descriptor: Elastase-1, 4-[[(2S)-3-methyl-1-oxo-1-[(2S)-2-[[(3S)-1,1,1-trifluoro-4-methyl-2-oxo-pentan-3-yl]carbamoyl]pyrrolidin-1-yl]butan-2-yl]carbamoyl]benzoic acid, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: chymotrypsin family, hydrolase, serine protease, calcium, disulfide bond, metal-binding, protease, secreted, zymogen
• Biological source: Sus scrofa (pig)
• Cellular location: Secreted: P00772
• Total number of polymer chains: 1
• Total formula weight: 26578.66

Authors

Tamada, T.,Kinoshita, T.,Kuroki, R.,Tada, T. (deposition date: 2009-05-14, release date: 2009-07-28, Last modification date: 2024-10-09)

Primary citation

Tamada, T.,Kinoshita, T.,Kurihara, K.,Adachi, M.,Ohhara, T.,Imai, K.,Kuroki, R.,Tada, T.
Combined High-Resolution Neutron and X-ray Analysis of Inhibited Elastase Confirms the Active-Site Oxyanion Hole but Rules against a Low-Barrier Hydrogen Bond
J.Am.Chem.Soc., 131:11033-11040, 2009

PubMed Abstract: To help resolve long-standing questions regarding the catalytic activity of the serine proteases, the structure of porcine pancreatic elastase has been analyzed by high-resolution neutron and X-ray crystallography. To mimic the tetrahedral transition intermediate, a peptidic inhibitor was used. A single large crystal was used to collect room-temperature neutron data to 1.65 A resolution and X-ray data to 1.20 A resolution. Another crystal provided a low-temperature X-ray data set to 0.94 A resolution. The neutron data are to higher resolution than previously reported for a serine protease and the X-ray data are comparable with other studies. The neutron and X-ray data show that the hydrogen bond between His57 and Asp102 (chymotrypsin numbering) is 2.60 A in length and that the hydrogen-bonding hydrogen is 0.80-0.96 A from the histidine nitrogen. This is not consistent with a low-barrier hydrogen which is predicted to have the hydrogen midway between the donor and acceptor atom. The observed interaction between His57 and Asp102 is essentially a short but conventional hydrogen bond, sometimes described as a short ionic hydrogen bond. The neutron analysis also shows that the oxygen of the oxopropyl group of the inhibitor is present as an oxygen anion rather than a hydroxyl group, supporting the role of the "oxyanion hole" in stabilizing the tetrahedral intermediate in catalysis.

PubMed: 19603802
DOI: 10.1021/ja9028846

Experimental method

X-RAY DIFFRACTION (0.94 Å)