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1a3b

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[[Image:1a3b.gif|left|200px]]<br /><applet load="1a3b" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1a3b, resolution 1.8&Aring;" />
 
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'''COMPLEX OF HUMAN ALPHA-THROMBIN WITH THE BIFUNCTIONAL BORONATE INHIBITOR BOROLOG1'''<br />
 
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==Overview==
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==COMPLEX OF HUMAN ALPHA-THROMBIN WITH THE BIFUNCTIONAL BORONATE INHIBITOR BOROLOG1==
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The crystal structure of the complexes of hirutonin-2 and hirutonin-6 with human alpha-thrombin have been solved and refined to R-factors of 0.169 (2.0 A resolution) and 0.162 (2.1 A), respectively. Hirutonins belong to a family of bifunctional inhibitors bearing a noncleavable moiety mimicking the scissile bond. Hirutonin-2 is an analog of (D)Phe-Pro-Arg-Gly-hirudin49-65; hirutonin-6 has the same N-terminal tripeptide connected to a shortened fibrinogen exosite-binding part by a short, nonpeptidyl linker. The hirutonin-6 molecule is well defined in the electron density with the exception of the C-terminal Leu-h61. The linker follows near the bottom of the canyon connecting the active site with the exosite, forms a short antiparallel beta-sheet-like arrangement with Leu40-Leu41 and makes van der Waals contacts with Glu39-Leu40-Leu41 of thrombin. In the thrombin-hirutonin-2 complex, the N- and C-terminal parts of the inhibitor are well ordered (except the C-terminal Gln-h65) while the central portion of the linker is partially disordered. The glycine analog in the P1' position of hirutonin-2 assumes a conformation similar to that of the canonical form (Bode and Huber (1992) Eur. J. Biochem. 204:433-451) and supports the identification of the S1' site as restricted by His57, Trp60D, Lys60F, and the Cys42-Cys58 disulfide bridge. The carbonyl oxygen of the P1 arginine residue is located in the oxyanion hole formed by the NH groups of Gly193 and Ser195, while the carbonyl carbon is positioned within a short distance, 2.8 A, from the O gamma of Ser195. This resembles the conformation of the substrate-like inhibitors bound to other serine proteases. The N-terminal (D)Phe-Pro-Arg fragment common to both inhibitors binds to thrombin in a fashion very similar to that of other inhibitors having this motif. The binding of the C-terminus of hirutonins to the fibrinogen-binding exosite is similar to that observed in hirudin and hirulog complexes.
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<StructureSection load='1a3b' size='340' side='right'caption='[[1a3b]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1a3b]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Hirudo_medicinalis Hirudo medicinalis] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1A3B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1A3B 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]] 1.8&#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=T29:TRI166+(BIFUNCTIONAL+BORONATE+INHIBITOR)'>T29</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=1a3b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1a3b OCA], [https://pdbe.org/1a3b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1a3b RCSB], [https://www.ebi.ac.uk/pdbsum/1a3b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1a3b ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/HIR2_HIRME HIR2_HIRME] Hirudin is a potent thrombin-specific protease inhibitor. It forms a stable non-covalent complex with alpha-thrombin, thereby abolishing its ability to cleave fibrinogen.
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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/a3/1a3b_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=1a3b ConSurf].
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<div style="clear:both"></div>
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==Disease==
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==See Also==
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Known diseases associated with this structure: Dysprothrombinemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176930 176930]], Hyperprothrombinemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176930 176930]], Hypoprothrombinemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176930 176930]]
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*[[Hirudin 3D structures|Hirudin 3D structures]]
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*[[Thrombin 3D Structures|Thrombin 3D Structures]]
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==About this Structure==
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__TOC__
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1A3B is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Hirudo_medicinalis Hirudo medicinalis] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=T29:'>T29</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. 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://oca.weizmann.ac.il/oca-bin/ocashort?id=1A3B OCA].
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</StructureSection>
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==Reference==
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Crystal structure of the complex of human alpha-thrombin and nonhydrolyzable bifunctional inhibitors, hirutonin-2 and hirutonin-6., Zdanov A, Wu S, DiMaio J, Konishi Y, Li Y, Wu X, Edwards BF, Martin PD, Cygler M, Proteins. 1993 Nov;17(3):252-65. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=8272424 8272424]
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[[Category: Hirudo medicinalis]]
[[Category: Hirudo medicinalis]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Thrombin]]
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[[Category: Deadman J]]
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[[Category: Deadman, J.]]
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[[Category: Dodson G]]
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[[Category: Dodson, G.]]
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[[Category: Elgendy S]]
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[[Category: Elgendy, S.]]
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[[Category: Freyssinet JH]]
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[[Category: Freyssinet, J H.]]
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[[Category: Goodwin CA]]
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[[Category: Goodwin, C A.]]
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[[Category: Green D]]
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[[Category: Green, D.]]
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[[Category: Kakkar VV]]
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[[Category: Kakkar, V V.]]
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[[Category: Scully MF]]
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[[Category: Scully, M F.]]
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[[Category: Skordalakes E]]
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[[Category: Skordalakes, E.]]
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[[Category: T29]]
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[[Category: complex (serine protease/inhibitor)]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:40:27 2008''
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Current revision

COMPLEX OF HUMAN ALPHA-THROMBIN WITH THE BIFUNCTIONAL BORONATE INHIBITOR BOROLOG1

PDB ID 1a3b

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