1PPH

GEOMETRY OF BINDING OF THE NALPHA-TOSYLATED PIPERIDIDES OF M-AMIDINO-, P-AMIDINO-AND P-GUANIDINO PHENYLALANINE TO THROMBIN AND TRYPSIN: X-RAY CRYSTAL STRUCTURES OF THEIR TRYPSIN COMPLEXES AND MODELING OF THEIR THROMBIN COMPLEXES

Summary for 1PPH

• Entry DOI: 10.2210/pdb1pph/pdb
• Related PRD ID: PRD_000374
• Descriptor: TRYPSIN, CALCIUM ION, SULFATE ION, ... (5 entities in total)
• Functional Keywords: serine proteinase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Sus scrofa (pig)
• Cellular location: Secreted, extracellular space: P00760
• Total number of polymer chains: 1
• Total formula weight: 23888.98

Authors

Bode, W.,Turk, D. (deposition date: 1991-10-24, release date: 1994-01-31, Last modification date: 2024-10-16)

Primary citation

Turk, D.,Sturzebecher, J.,Bode, W.
Geometry of binding of the N alpha-tosylated piperidides of m-amidino-, p-amidino- and p-guanidino phenylalanine to thrombin and trypsin. X-ray crystal structures of their trypsin complexes and modeling of their thrombin complexes.
FEBS Lett., 287:133-138, 1991

PubMed Abstract: The X-ray crystal structures of the complexes formed with bovine trypsin and the N alpha-tosylated piperidides of m-amidino-, p-amidino- and p-guanidino-D,L-phenylalanine (3-TAPAP, 4-TAPAP and 4-TGPAP) were determined with data to 1.8 A resolution. The L-stereoisomer of 3-TAPAP binds as a compact entity into the active site of trypsin, with the amidino and the carbonyl groups of the central amidinophenylalanyl residue hydrogen-bonded to Gly216 of trypsin. According to modeling and energy minimization, 3-TAPAP fits perfectly in this conformation to the more restrictive thrombin active site also (Bajusz et al. (1978) Int. J. Pept. Prot. Res. 12, 217-221); the piperidine moiety extends into the cage-like S2 subsite of thrombin, but leaves room for additional substituents which might help to improve binding and pharmacological properties. In contrast, 4-TAPAP and 4-TGPAP bind only weakly and in an extended conformation to trypsin; their considerably enhanced affinities for thrombin would suggest a more compact binding to thrombin.

PubMed: 1879520
DOI: 10.1016/0014-5793(91)80033-Y

Experimental method

X-RAY DIFFRACTION (1.9 Å)