1ppc
From Proteopedia
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| - | [[Image:1ppc.gif|left|200px]] | + | [[Image:1ppc.gif|left|200px]] |
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| - | '''GEOMETRY OF BINDING OF THE BENZAMIDINE-AND ARGININE-BASED INHIBITORS N-ALPHA-(2-NAPHTHYL-SULPHONYL-GLYCYL)-DL-P-AMIDINOPHENYLALANYL-PIPERIDINE (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''' | + | {{Structure |
| + | |PDB= 1ppc |SIZE=350|CAPTION= <scene name='initialview01'>1ppc</scene>, resolution 1.8Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene> and <scene name='pdbligand=NAS:2-NAPHTHALENESULFONIC ACID'>NAS</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Trypsin Trypsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.4 3.4.21.4] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''GEOMETRY OF BINDING OF THE BENZAMIDINE-AND ARGININE-BASED INHIBITORS N-ALPHA-(2-NAPHTHYL-SULPHONYL-GLYCYL)-DL-P-AMIDINOPHENYLALANYL-PIPERIDINE (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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==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1PPC is a [ | + | 1PPC is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PPC OCA]. |
==Reference== | ==Reference== | ||
| - | 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., Bode W, Turk D, Sturzebecher J, Eur J Biochem. 1990 Oct 5;193(1):175-82. PMID:[http:// | + | 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., Bode W, Turk D, Sturzebecher J, Eur J Biochem. 1990 Oct 5;193(1):175-82. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/2226434 2226434] |
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Trypsin]] | [[Category: Trypsin]] | ||
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[[Category: hydrolase(serine proteinase)]] | [[Category: hydrolase(serine proteinase)]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:27:15 2008'' |
Revision as of 11:27, 20 March 2008
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| , resolution 1.8Å | |||||||
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| Ligands: | and | ||||||
| Activity: | Trypsin, with EC number 3.4.21.4 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
GEOMETRY OF BINDING OF THE BENZAMIDINE-AND ARGININE-BASED INHIBITORS N-ALPHA-(2-NAPHTHYL-SULPHONYL-GLYCYL)-DL-P-AMIDINOPHENYLALANYL-PIPERIDINE (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
Overview
The X-ray crystal structure of the trypsin complex formed with N alpha-(2-naphthyl-sulphonyl-glycyl)-DL-p-amidinophenylalanyl-piper idine (NAPAP) was determined with X-ray data to 0.18-nm resolution and crystallographically refined. NAPAP binds into the active site of trypsin in a quite compact form: the p-amidinophenylalanine moiety of the D-stereoisomer binds into the specificity pocket; the glycyl group is hydrogen bonded with Gly216; the naphthyl group stands perpendicular to the indole moiety of Trp215; the piperidine ring is tightly packed between this naphthyl moiety and His57; in consequence the carboxy-terminal amido bond of NAPAP is located in such a way that it is not susceptible to the active-site Ser195. 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) [Matzusaki, T., Sasaki, C., Okumura, C. & Umeyama (1989) J. Biochem. (Tokyo) 105, 949-952] were transferred in their trypsin-binding conformations to human alpha-thrombin [Bode, W., Mayr, I., Baumann, U., Huber, R., Stone, S. R. & Hofsteenge, J. (1989) EMBO J. 8. 3467 - 3475] and energy minimized. Both synthetic inhibitors fit perfectly into the much more restricted active site of thrombin. The accommodation of the S-aryl moieties in the 'aryl-binding site' and of the piperidine rings in the S2 subsite of thrombin are particularly favorable. The preference of thrombin for distinctly substituted piperidine derivatives and its generally higher (compared with trypsin) affinity for benzamidine and arginine-based inhibitors can be accounted for by these thrombin inhibitor models.
About this Structure
1PPC is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.
Reference
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., Bode W, Turk D, Sturzebecher J, Eur J Biochem. 1990 Oct 5;193(1):175-82. PMID:2226434
Page seeded by OCA on Thu Mar 20 13:27:15 2008
Categories: Single protein | Trypsin | Bode, W. | Turk, D. | CA | NAS | Hydrolase(serine proteinase)
