1xs7

From Proteopedia

(Difference between revisions)

Revision as of 07:01, 18 April 2018

Crystal Structure of a cycloamide-urethane-derived novel inhibitor bound to human brain memapsin 2 (beta-secretase).

Structural highlights

1xs7 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	BACE1, BACE (HUMAN)
Activity:	Memapsin 2, with EC number 3.4.23.46
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 series of novel macrocyclic amide-urethanes was designed and synthesized based upon the X-ray crystal structure of our lead inhibitor (1, OM99-2 with eight residues) bound to memapsin 2. Ring size and substituent effects have been investigated. Cycloamide-urethanes containing 14- to 16-membered rings exhibited low nanomolar inhibitory potencies against human brain memapsin 2 (beta-secretase).

Structure-based design of cycloamide-urethane-derived novel inhibitors of human brain memapsin 2 (beta-secretase).,Ghosh AK, Devasamudram T, Hong L, DeZutter C, Xu X, Weerasena V, Koelsch G, Bilcer G, Tang J Bioorg Med Chem Lett. 2005 Jan 3;15(1):15-20. PMID:15582402^[3]

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

References

↑ 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
↑ 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
↑ Ghosh AK, Devasamudram T, Hong L, DeZutter C, Xu X, Weerasena V, Koelsch G, Bilcer G, Tang J. Structure-based design of cycloamide-urethane-derived novel inhibitors of human brain memapsin 2 (beta-secretase). Bioorg Med Chem Lett. 2005 Jan 3;15(1):15-20. PMID:15582402 doi:10.1016/j.bmcl.2004.10.084

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1xs7"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of a cycloamide-urethane-derived novel inhibitor bound to human brain memapsin 2 (beta-secretase).==
 <StructureSection load='1xs7' size='340' side='right' caption='[[1xs7]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BACE1, BACE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Memapsin_2 Memapsin 2], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1xs7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xs7 OCA], [http://pdbe.org/1xs7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1xs7 RCSB], [http://www.ebi.ac.uk/pdbsum/1xs7 PDBsum]</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=1xs7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xs7 OCA], [http://pdbe.org/1xs7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1xs7 RCSB], [http://www.ebi.ac.uk/pdbsum/1xs7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1xs7 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xs/1xs7_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xs/1xs7_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/chain_selection.php?pdb_ID=2ata ConSurf].
+</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=1xs7 ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">

1xs7

From Proteopedia

Revision as of 07:01, 18 April 2018

Crystal Structure of a cycloamide-urethane-derived novel inhibitor bound to human brain memapsin 2 (beta-secretase).

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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