2vnm

From Proteopedia

(Difference between revisions)

Revision as of 21:28, 19 September 2018

Human BACE-1 in complex with 3-(1,1-dioxidotetrahydro-2H-1,2-thiazin- 2-yl)-5-(ethylamino)-N-((1S,2R)-2-hydroxy-1-(phenylmethyl)-3-(((3-(trifluoromethyl)phenyl)methyl)amino)propyl)benzamide

Structural highlights

2vnm 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:
Related:	1tqf, 1xn3, 1m4h, 1xn2, 2viy, 2vie, 2va6, 2vj6, 2viz, 2b8l, 1ym4, 1sgz, 2va5, 1ujk, 2b8v, 1fkn, 1xs7, 2vij, 2va7, 1ym2, 2vkm, 2vj9, 2vnn, 1py1, 1w50, 1ujj, 2vj7, 1w51
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

BACE-1 inhibition has the potential to provide a disease-modifying therapy for the treatment of Alzheimer's disease. Optimization of a first generation of BACE-1 inhibitors led to the discovery of novel hydroxyethylamines (HEAs) bearing a tricyclic nonprime side. These derivatives have nanomolar cell potency and are orally bioavailable.

Second Generation of Hydroxyethylamine BACE-1 Inhibitors: Optimizing Potency and Oral Bioavailability.,Charrier N, Clarke B, Cutler L, Demont E, Dingwall C, Dunsdon R, East P, Hawkins J, Howes C, Hussain I, Jeffrey P, Maile G, Matico R, Mosley J, Naylor A, O'Brien A, Redshaw S, Rowland P, Soleil V, Smith KJ, Sweitzer S, Theobald P, Vesey D, Walter DS, Wayne G J Med Chem. 2008 May 6;. PMID:18457381^[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
↑ Charrier N, Clarke B, Cutler L, Demont E, Dingwall C, Dunsdon R, East P, Hawkins J, Howes C, Hussain I, Jeffrey P, Maile G, Matico R, Mosley J, Naylor A, O'Brien A, Redshaw S, Rowland P, Soleil V, Smith KJ, Sweitzer S, Theobald P, Vesey D, Walter DS, Wayne G. Second Generation of Hydroxyethylamine BACE-1 Inhibitors: Optimizing Potency and Oral Bioavailability. J Med Chem. 2008 May 6;. PMID:18457381 doi:10.1021/jm800138h

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/2vnm"

@@ Line 1: / Line 1: @@
-==HUMAN BACE-1 IN COMPLEX WITH 3-(1,1-DIOXIDOTETRAHYDRO-2H-1, 2-THIAZIN-2-YL)-5-(ETHYLAMINO)-N-((1S,2R)-2-HYDROXY-1-(PHENYLMETHYL)-3-(((3-(TRIFLUOROMETHYL)PHENYL)METHYL)AMINO) PROPYL)BENZAMIDE==
+==Human BACE-1 in complex with 3-(1,1-dioxidotetrahydro-2H-1,2-thiazin- 2-yl)-5-(ethylamino)-N-((1S,2R)-2-hydroxy-1-(phenylmethyl)-3-(((3-(trifluoromethyl)phenyl)methyl)amino)propyl)benzamide==
 <StructureSection load='2vnm' size='340' side='right' caption='[[2vnm]], [[Resolution|resolution]] 1.79&Aring;' scene=''>
 == Structural highlights ==
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1tqf|1tqf]], [[1xn3|1xn3]], [[1m4h|1m4h]], [[1xn2|1xn2]], [[2viy|2viy]], [[2vie|2vie]], [[2va6|2va6]], [[2vj6|2vj6]], [[2viz|2viz]], [[2b8l|2b8l]], [[1ym4|1ym4]], [[1sgz|1sgz]], [[2va5|2va5]], [[1ujk|1ujk]], [[2b8v|2b8v]], [[1fkn|1fkn]], [[1xs7|1xs7]], [[2vij|2vij]], [[2va7|2va7]], [[1ym2|1ym2]], [[2vkm|2vkm]], [[2vj9|2vj9]], [[2vnn|2vnn]], [[1py1|1py1]], [[1w50|1w50]], [[1ujj|1ujj]], [[2vj7|2vj7]], [[1w51|1w51]]</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=2vnm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vnm OCA], [http://pdbe.org/2vnm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2vnm RCSB], [http://www.ebi.ac.uk/pdbsum/2vnm 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=2vnm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vnm OCA], [http://pdbe.org/2vnm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2vnm RCSB], [http://www.ebi.ac.uk/pdbsum/2vnm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2vnm 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/vn/2vnm_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vn/2vnm_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 53: / Line 54: @@
 [[Category: Mosley, J]]
 [[Category: Naylor, A]]
-[[Category: Obrien, A]]
+[[Category: OBrien, A]]
 [[Category: Redshaw, S]]
 [[Category: Rowland, P]]
@@ Line 63: / Line 64: @@
 [[Category: Walter, D S]]
 [[Category: Wayne, G]]
+[[Category: Alternative splicing]]
 [[Category: Asp-2]]
 [[Category: Aspartyl protease]]

2vnm

From Proteopedia

Revision as of 21:28, 19 September 2018

Human BACE-1 in complex with 3-(1,1-dioxidotetrahydro-2H-1,2-thiazin- 2-yl)-5-(ethylamino)-N-((1S,2R)-2-hydroxy-1-(phenylmethyl)-3-(((3-(trifluoromethyl)phenyl)methyl)amino)propyl)benzamide

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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