1pph
From Proteopedia
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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
Overview
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.
About this Structure
1PPH is a Single protein structure of sequence from [1] with CA, SO4, APM and TOS as ligands. Active as Trypsin, with EC number 3.4.21.4 Full crystallographic information is available from OCA.
Reference
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., Turk D, Sturzebecher J, Bode W, FEBS Lett. 1991 Aug 5;287(1-2):133-8. PMID:1879520
Page seeded by OCA on Tue Nov 20 23:59:53 2007
Categories: Single protein | Trypsin | Bode, W. | Turk, D. | APM | CA | SO4 | TOS | Hydrolase(serine proteinase)
