2xfj

From Proteopedia

(Difference between revisions)

Revision as of 08:39, 10 November 2021

Human BACE-1 in complex with N-((1S,2R)-3-(((1S)-2-(cyclohexylamino)- 1-methyl-2-oxoethyl)amino)-2-hydroxy-1-(phenylmethyl)propyl)-3-(ethylamino)-5-(2-oxo-1-pyrrolidinyl)benzamide

Structural highlights

2xfj 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:	1xn3, 2wf3, 2wf1, 2vnm, 2wf4, 2fdp, 2vj6, 2wf2, 1ym4, 1sgz, 1ujk, 2va7, 2wjo, 2wez, 1ym2, 1py1, 1w50, 2vj7, 2wf0, 1w51, 1tqf, 1m4h, 1xn2, 2viy, 2va6, 2vie, 2viz, 2b8l, 2va5, 2b8v, 1fkn, 1xs7, 2vij, 2vkm, 2vj9, 2vnn, 1ujj, 2xfi, 2xfk
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

Inhibition of the aspartyl protease BACE-1 has the potential to deliver a disease-modifying therapy for Alzheimer's disease. Herein, is described a series of potent inhibitors based on an hydroxyethylamine (HEA) transition state mimetic template. These inhibitors interact with the non prime side of the enzyme using a novel edge-to-face interaction with Arg-296.

BACE-1 hydroxyethylamine inhibitors using novel edge-to-face interaction with Arg-296.,Clarke B, Cutler L, Demont E, Dingwall C, Dunsdon R, Hawkins J, Howes C, Hussain I, 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 Bioorg Med Chem Lett. 2010 Aug 1;20(15):4639-44. Epub 2010 Jun 8. PMID:20579874^[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
↑ Clarke B, Cutler L, Demont E, Dingwall C, Dunsdon R, Hawkins J, Howes C, Hussain I, 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. BACE-1 hydroxyethylamine inhibitors using novel edge-to-face interaction with Arg-296. Bioorg Med Chem Lett. 2010 Aug 1;20(15):4639-44. Epub 2010 Jun 8. PMID:20579874 doi:10.1016/j.bmcl.2010.05.111

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/2xfj"

@@ Line 3: / Line 3: @@
 <StructureSection load='2xfj' size='340' side='right'caption='[[2xfj]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2xfj]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XFJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XFJ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2xfj]] 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=2XFJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XFJ FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=VG5:N-[(1S,2R)-1-BENZYL-3-{[(1S)-2-(CYCLOHEXYLAMINO)-1-METHYL-2-OXOETHYL]AMINO}-2-HYDROXYPROPYL]-3-(ETHYLAMINO)-5-(2-OXOPYRROLIDIN-1-YL)BENZAMIDE'>VG5</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=VG5:N-[(1S,2R)-1-BENZYL-3-{[(1S)-2-(CYCLOHEXYLAMINO)-1-METHYL-2-OXOETHYL]AMINO}-2-HYDROXYPROPYL]-3-(ETHYLAMINO)-5-(2-OXOPYRROLIDIN-1-YL)BENZAMIDE'>VG5</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1xn3|1xn3]], [[2wf3|2wf3]], [[2wf1|2wf1]], [[2vnm|2vnm]], [[2wf4|2wf4]], [[2fdp|2fdp]], [[2vj6|2vj6]], [[2wf2|2wf2]], [[1ym4|1ym4]], [[1sgz|1sgz]], [[1ujk|1ujk]], [[2va7|2va7]], [[2wjo|2wjo]], [[2wez|2wez]], [[1ym2|1ym2]], [[1py1|1py1]], [[1w50|1w50]], [[2vj7|2vj7]], [[2wf0|2wf0]], [[1w51|1w51]], [[1tqf|1tqf]], [[1m4h|1m4h]], [[1xn2|1xn2]], [[2viy|2viy]], [[2va6|2va6]], [[2vie|2vie]], [[2viz|2viz]], [[2b8l|2b8l]], [[2va5|2va5]], [[2b8v|2b8v]], [[1fkn|1fkn]], [[1xs7|1xs7]], [[2vij|2vij]], [[2vkm|2vkm]], [[2vj9|2vj9]], [[2vnn|2vnn]], [[1ujj|1ujj]], [[2xfi|2xfi]], [[2xfk|2xfk]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1xn3|1xn3]], [[2wf3|2wf3]], [[2wf1|2wf1]], [[2vnm|2vnm]], [[2wf4|2wf4]], [[2fdp|2fdp]], [[2vj6|2vj6]], [[2wf2|2wf2]], [[1ym4|1ym4]], [[1sgz|1sgz]], [[1ujk|1ujk]], [[2va7|2va7]], [[2wjo|2wjo]], [[2wez|2wez]], [[1ym2|1ym2]], [[1py1|1py1]], [[1w50|1w50]], [[2vj7|2vj7]], [[2wf0|2wf0]], [[1w51|1w51]], [[1tqf|1tqf]], [[1m4h|1m4h]], [[1xn2|1xn2]], [[2viy|2viy]], [[2va6|2va6]], [[2vie|2vie]], [[2viz|2viz]], [[2b8l|2b8l]], [[2va5|2va5]], [[2b8v|2b8v]], [[1fkn|1fkn]], [[1xs7|1xs7]], [[2vij|2vij]], [[2vkm|2vkm]], [[2vj9|2vj9]], [[2vnn|2vnn]], [[1ujj|1ujj]], [[2xfi|2xfi]], [[2xfk|2xfk]]</div></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='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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2xfj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xfj OCA], [http://pdbe.org/2xfj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2xfj RCSB], [http://www.ebi.ac.uk/pdbsum/2xfj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2xfj 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=2xfj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xfj OCA], [https://pdbe.org/2xfj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xfj RCSB], [https://www.ebi.ac.uk/pdbsum/2xfj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xfj ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://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 ==
 [[Image:Consurf_key_small.gif|200px|right]]

2xfj

From Proteopedia

Revision as of 08:39, 10 November 2021

Human BACE-1 in complex with N-((1S,2R)-3-(((1S)-2-(cyclohexylamino)- 1-methyl-2-oxoethyl)amino)-2-hydroxy-1-(phenylmethyl)propyl)-3-(ethylamino)-5-(2-oxo-1-pyrrolidinyl)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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