1m4h

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{{Seed}}
 
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[[Image:1m4h.png|left|200px]]
 
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==Crystal Structure of Beta-secretase complexed with Inhibitor OM00-3==
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The line below this paragraph, containing "STRUCTURE_1m4h", creates the "Structure Box" on the page.
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<StructureSection load='1m4h' size='340' side='right'caption='[[1m4h]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1m4h]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. The July 2009 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''beta-Secretase'' by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2009_7 10.2210/rcsb_pdb/mom_2009_7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M4H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1M4H 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]] 2.1&#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=1OL:(2R,4S,5S)-5-AMINO-4-HYDROXY-2,7-DIMETHYLOCTANOIC+ACID'>1OL</scene></td></tr>
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{{STRUCTURE_1m4h| PDB=1m4h | SCENE= }}
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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=1m4h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m4h OCA], [https://pdbe.org/1m4h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1m4h RCSB], [https://www.ebi.ac.uk/pdbsum/1m4h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1m4h ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/BACE1_HUMAN BACE1_HUMAN] Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase.<ref>PMID:10677483</ref> <ref>PMID:20354142</ref>
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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/m4/1m4h_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1m4h ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The structure of the catalytic domain of human memapsin 2 bound to an inhibitor OM00-3 (Glu-Leu-Asp-LeuAla-Val-Glu-Phe, K(i) = 0.3 nM, the asterisk denotes the hydroxyethylene transition-state isostere) has been determined at 2.1 A resolution. Uniquely defined in the structure are the locations of S(3)' and S(4)' subsites, which were not identified in the previous structure of memapsin 2 in complex with the inhibitor OM99-2 (Glu-Val-Asn-LeuAla-Ala-Glu-Phe, K(i) = 1 nM). Different binding modes for the P(2) and P(4) side chains are also observed. These new structural elements are useful for the design of new inhibitors. The structural and kinetic data indicate that the replacement of the P(2)' alanine in OM99-2 with a valine in OM00-3 stabilizes the binding of P(3)' and P(4)'.
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===Crystal Structure of Beta-secretase complexed with Inhibitor OM00-3===
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Crystal structure of memapsin 2 (beta-secretase) in complex with an inhibitor OM00-3.,Hong L, Turner RT 3rd, Koelsch G, Shin D, Ghosh AK, Tang J Biochemistry. 2002 Sep 10;41(36):10963-7. PMID:12206667<ref>PMID:12206667</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 1m4h" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_12206667}}, adds the Publication Abstract to the page
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*[[Beta secretase 3D structures|Beta secretase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 12206667 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_12206667}}
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__TOC__
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</StructureSection>
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==About this Structure==
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1M4H is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M4H OCA].
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==Reference==
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Crystal structure of memapsin 2 (beta-secretase) in complex with an inhibitor OM00-3., Hong L, Turner RT 3rd, Koelsch G, Shin D, Ghosh AK, Tang J, Biochemistry. 2002 Sep 10;41(36):10963-7. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12206667 12206667]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Ghosh, A K.]]
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[[Category: RCSB PDB Molecule of the Month]]
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[[Category: Hong, L.]]
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[[Category: Synthetic construct]]
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[[Category: Koelsch, G.]]
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[[Category: Beta-Secretase]]
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[[Category: Tang, J.]]
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[[Category: Ghosh AK]]
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[[Category: Turner, R T.]]
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[[Category: Hong L]]
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[[Category: Acid protease]]
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[[Category: Koelsch G]]
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[[Category: Alzheimer's disease]]
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[[Category: Tang J]]
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[[Category: Asp2]]
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[[Category: Turner RT]]
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[[Category: Aspartic protease]]
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[[Category: Base]]
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[[Category: Beta-secretase]]
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[[Category: Memapsin2]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 23:11:25 2008''
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Current revision

Crystal Structure of Beta-secretase complexed with Inhibitor OM00-3

PDB ID 1m4h

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