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PDBsum entry 1pph
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Hydrolase/hydrolase inhibitor
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PDB id
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1pph
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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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.
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Authors
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D.Turk,
J.Stürzebecher,
W.Bode.
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Ref.
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FEBS Lett, 1991,
287,
133-138.
[DOI no: ]
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PubMed id
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Abstract
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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.
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Secondary reference #1
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Title
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Geometry of binding of the benzamidine- And arginine-Based inhibitors n alpha-(2-Naphthyl-Sulphonyl-Glycyl)-Dl-P-Amidinophenylalanyl-Pipe ridine (napap) and (2r,4r)-4-Methyl-1-[N alpha-(3-Methyl-1,2,3,4-Tetrahydro-8- Quinolinesulphonyl)-L-Arginyl]-2-Piperidine carboxylic acid (mqpa) to human alpha-Thrombin. X-Ray crystallographic determination of the napap-Trypsin complex and modeling of napap-Thrombin and mqpa-Thrombin.
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Authors
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W.Bode,
D.Turk,
J.Stürzebecher.
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Ref.
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Eur J Biochem, 1990,
193,
175-182.
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PubMed id
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Secondary reference #2
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Title
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The refined 1.9 a crystal structure of human alpha-Thrombin: interaction with d-Phe-Pro-Arg chloromethylketone and significance of the tyr-Pro-Pro-Trp insertion segment.
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Authors
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W.Bode,
I.Mayr,
U.Baumann,
R.Huber,
S.R.Stone,
J.Hofsteenge.
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Ref.
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Embo J, 1989,
8,
3467-3475.
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PubMed id
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