1a0h

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(New page: 200px<br /> <applet load="1a0h" size="450" color="white" frame="true" align="right" spinBox="true" caption="1a0h, resolution 3.2&Aring;" /> '''THE X-RAY CRYSTAL ST...)
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[[Image:1a0h.gif|left|200px]]<br />
 
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<applet load="1a0h" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1a0h, resolution 3.2&Aring;" />
 
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'''THE X-RAY CRYSTAL STRUCTURE OF PPACK-MEIZOTHROMBIN DESF1: KRINGLE/THROMBIN AND CARBOHYDRATE/KRINGLE/THROMBIN INTERACTIONS AND LOCATION OF THE LINKER CHAIN'''<br />
 
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==Overview==
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==THE X-RAY CRYSTAL STRUCTURE OF PPACK-MEIZOTHROMBIN DESF1: KRINGLE/THROMBIN AND CARBOHYDRATE/KRINGLE/THROMBIN INTERACTIONS AND LOCATION OF THE LINKER CHAIN==
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BACKGROUND: The conversion of prothrombin to thrombin by factor Xa is the, penultimate step in the blood clotting cascade. In vivo, where the, conversion occurs primarily on activated platelets in association with, factor Va and Ca2+ ions, meizothrombin is the major intermediate of the, two step reaction. Meizothrombin rapidly loses the fragment 1 domain (F1), by autolysis to become meizothrombin des F1 (mzTBN-F1). The physiological, properties of mzTBN-F1 differ dramatically from those of thrombin due to, the presence of prothrombin fragment 2 (F2), which remains covalently, attached to the activated thrombin domain in mzTBN-F1. RESULTS: The, crystal structure of mzTBN-F1 has been determined at 3.1 A resolution by, molecular replacement, using only the thrombin domain, and refined to R, and Rfree values of 0.205 and 0.242, respectively. The protease active, site was inhibited with D-Phe-Pro-Arg-chloromethylketone (PPACK) to reduce, autolysis. The mobile linker chain connecting the so-called kringle and, thrombin domains and the first two N-acetylglucosamine residues attached, to the latter were seen in electron-density maps improved with the program, SQUASH. Previously these regions had only been modeled. CONCLUSIONS: The, F2 kringle domain in mzTBN-F1 is bound to the electropositive, heparin-binding site on thrombin in an orientation that is systematically, shifted and has significantly more interdomain contacts compared to a, noncovalent complex of free F2 and free thrombin. F2 in mzTBN-F1 forms, novel hydrogen bonds to the carbohydrate chain of thrombin and perhaps, stabilizes a unique, rigid conformation of the gamma-autolysis loop, through non-local effects. The F2 linker chain, which does not interfere, with the active site or fibrinogen-recognition site, is arranged so that, the two sites cleaved by factor Xa are separated by 36 A. The two mzTBN-F1, molecules in the asymmetric unit share a tight 'dimer' contact in which, the active site of one molecule is partially blocked by the F2 kringle, domain of its partner. This interaction suggests a new model for, prothrombin organization.
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<StructureSection load='1a0h' size='340' side='right'caption='[[1a0h]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1a0h]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. The January 2002 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Thrombin'' by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2002_1 10.2210/rcsb_pdb/mom_2002_1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1A0H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1A0H FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0G6:D-PHENYLALANYL-N-[(2S,3S)-6-{[AMINO(IMINIO)METHYL]AMINO}-1-CHLORO-2-HYDROXYHEXAN-3-YL]-L-PROLINAMIDE'>0G6</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1a0h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1a0h OCA], [https://pdbe.org/1a0h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1a0h RCSB], [https://www.ebi.ac.uk/pdbsum/1a0h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1a0h ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/THRB_BOVIN THRB_BOVIN] Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing (By similarity).
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a0/1a0h_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1a0h ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1A0H is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with CH2 as [http://en.wikipedia.org/wiki/ligand ligand]. The following page contains interesting information on the relation of 1A0H with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb25_1.html Thrombin]]. Active as [http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1A0H OCA].
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*[[Thrombin 3D Structures|Thrombin 3D Structures]]
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__TOC__
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==Reference==
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</StructureSection>
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New insights into the regulation of the blood clotting cascade derived from the X-ray crystal structure of bovine meizothrombin des F1 in complex with PPACK., Martin PD, Malkowski MG, Box J, Esmon CT, Edwards BF, Structure. 1997 Dec 15;5(12):1681-93. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9438869 9438869]
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[[Category: Bos taurus]]
[[Category: Bos taurus]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: RCSB PDB Molecule of the Month]]
[[Category: Thrombin]]
[[Category: Thrombin]]
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[[Category: Box, J.]]
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[[Category: Box J]]
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[[Category: Edwards, B.F.P.]]
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[[Category: Edwards BFP]]
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[[Category: Esmon, C.T.]]
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[[Category: Esmon CT]]
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[[Category: Malkowski, M.G.]]
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[[Category: Malkowski MG]]
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[[Category: Martin, P.D.]]
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[[Category: Martin PD]]
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[[Category: CH2]]
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[[Category: coagulation]]
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[[Category: complex (serine protease/inhibitor)]]
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[[Category: meizothrombin]]
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[[Category: prothrombin]]
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[[Category: serine protease]]
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[[Category: thrombin]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Sun Nov 18 08:56:30 2007''
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Current revision

THE X-RAY CRYSTAL STRUCTURE OF PPACK-MEIZOTHROMBIN DESF1: KRINGLE/THROMBIN AND CARBOHYDRATE/KRINGLE/THROMBIN INTERACTIONS AND LOCATION OF THE LINKER CHAIN

PDB ID 1a0h

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