3exo: Difference between revisions

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<StructureSection load='3exo' size='340' side='right'caption='[[3exo]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
<StructureSection load='3exo' size='340' side='right'caption='[[3exo]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3exo]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EXO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3EXO FirstGlance]. <br>
<table><tr><td colspan='2'>[[3exo]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3EXO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3EXO FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5MS:N-{2-METHYL-5-[(6-PHENYLPYRIMIDIN-4-YL)AMINO]PHENYL}METHANESULFONAMIDE'>5MS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
</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>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BACE1, BACE, KIAA1149 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5MS:N-{2-METHYL-5-[(6-PHENYLPYRIMIDIN-4-YL)AMINO]PHENYL}METHANESULFONAMIDE'>5MS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Memapsin_2 Memapsin 2], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.46 3.4.23.46] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3exo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3exo OCA], [https://pdbe.org/3exo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3exo RCSB], [https://www.ebi.ac.uk/pdbsum/3exo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3exo ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3exo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3exo OCA], [https://pdbe.org/3exo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3exo RCSB], [https://www.ebi.ac.uk/pdbsum/3exo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3exo ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[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>
[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>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Memapsin 2]]
[[Category: Allison TJ]]
[[Category: Allison, T J]]
[[Category: Aspartyl protease]]
[[Category: Bace 1]]
[[Category: Beta secretase]]
[[Category: Glycoprotein]]
[[Category: Hydrolase]]
[[Category: Membrane]]
[[Category: Protease]]
[[Category: Transmembrane]]
[[Category: Zymogen]]

Revision as of 03:26, 28 December 2023

Crystal structure of BACE1 bound to inhibitorCrystal structure of BACE1 bound to inhibitor

Structural highlights

3exo is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.1Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.[1] [2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

A small molecule inhibitor of beta-secretase with a unique binding mode has been developed. Crystallographic determination of the enzyme-inhibitor complex shows the catalytic aspartate residues in the active site are not engaged in inhibitor binding. This unprecedented binding mode in the field of aspartyl protease inhibition is described.

Identification of a small molecule beta-secretase inhibitor that binds without catalytic aspartate engagement.,Steele TG, Hills ID, Nomland AA, de Leon P, Allison T, McGaughey G, Colussi D, Tugusheva K, Haugabook SJ, Espeseth AS, Zuck P, Graham SL, Stachel SJ Bioorg Med Chem Lett. 2009 Jan 1;19(1):17-20. Epub 2008 Nov 13. PMID:19036583[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Lin X, Koelsch G, Wu S, Downs D, Dashti A, Tang J. Human aspartic protease memapsin 2 cleaves the beta-secretase site of beta-amyloid precursor protein. Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1456-60. PMID:10677483
  2. ↑ Okada H, Zhang W, Peterhoff C, Hwang JC, Nixon RA, Ryu SH, Kim TW. Proteomic identification of sorting nexin 6 as a negative regulator of BACE1-mediated APP processing. FASEB J. 2010 Aug;24(8):2783-94. doi: 10.1096/fj.09-146357. Epub 2010 Mar 30. PMID:20354142 doi:10.1096/fj.09-146357
  3. ↑ Steele TG, Hills ID, Nomland AA, de Leon P, Allison T, McGaughey G, Colussi D, Tugusheva K, Haugabook SJ, Espeseth AS, Zuck P, Graham SL, Stachel SJ. Identification of a small molecule beta-secretase inhibitor that binds without catalytic aspartate engagement. Bioorg Med Chem Lett. 2009 Jan 1;19(1):17-20. Epub 2008 Nov 13. PMID:19036583 doi:10.1016/j.bmcl.2008.11.027

3exo, resolution 2.10Å

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