View source for 1ppc


==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==
<StructureSection load='1ppc' size='340' side='right' caption='[[1ppc]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1ppc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PPC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1PPC FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MID:1-[N-(NAPHTHALEN-2-YLSULFONYL)GLYCYL-4-CARBAMIMIDOYL-D-PHENYLALANYL]PIPERIDINE'>MID</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ppc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ppc OCA], [http://pdbe.org/1ppc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ppc RCSB], [http://www.ebi.ac.uk/pdbsum/1ppc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1ppc ProSAT]</span></td></tr>
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== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pp/1ppc_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1ppc ConSurf].
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== Publication Abstract from PubMed ==
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. &amp; 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. &amp; 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.

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<ref>PMID:2226434</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bovin]]
[[Category: Trypsin]]
[[Category: Bode, W]]
[[Category: Turk, D]]
[[Category: Hydrolase-hydrolase inhibitor complex]]
[[Category: Serine proteinase]]