This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

2vkm

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 20:40, 24 December 2014

CRYSTAL STRUCTURE OF GRL-8234 BOUND TO BACE (BETA-SECRETASE)

Structural highlights

2vkm is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	1fkn, 1py1, 1tqf, 1ujj, 1ujk, 1xn2, 1xn3, 1ym2, 2b8l, 2b8v, 2va5, 2va6, 2va7, 2vie, 2vij, 2viy, 2vj7, 1m4h, 1sgz, 1w50, 1w51, 1xs7, 1ym4, 2viz, 2vj6
Resources:	FirstGlance, OCA, RCSB, PDBsum

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

Structure-based design, synthesis, and biological evaluation of a series of peptidomimetic beta-secretase inhibitors incorporating hydroxyethylamine isosteres are described. We have identified inhibitor 24 which has shown exceedingly potent activity in memapsin 2 enzyme inhibitory (K(i) 1.8 nM) and cellular (IC(50)=1 nM in Chinese hamster ovary cells) assays. Inhibitor 24 has also shown very impressive in vivo properties (up to 65% reduction of plasma A beta) in transgenic mice. The X-ray structure of protein-ligand complex of memapsin 2 revealed critical interactions in the memapsin 2 active site.

Potent memapsin 2 (beta-secretase) inhibitors: design, synthesis, protein-ligand X-ray structure, and in vivo evaluation.,Ghosh AK, Kumaragurubaran N, Hong L, Kulkarni S, Xu X, Miller HB, Reddy DS, Weerasena V, Turner R, Chang W, Koelsch G, Tang J Bioorg Med Chem Lett. 2008 Feb 1;18(3):1031-6. Epub 2008 Jan 3. PMID:18180160^[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, Kumaragurubaran N, Hong L, Kulkarni S, Xu X, Miller HB, Reddy DS, Weerasena V, Turner R, Chang W, Koelsch G, Tang J. Potent memapsin 2 (beta-secretase) inhibitors: design, synthesis, protein-ligand X-ray structure, and in vivo evaluation. Bioorg Med Chem Lett. 2008 Feb 1;18(3):1031-6. Epub 2008 Jan 3. PMID:18180160 doi:S0960-894X(07)01473-4

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/2vkm"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2vkm]] is a 4 chain structure with 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=2VKM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2VKM FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BSD:N-{(1S,2R)-1-BENZYL-2-HYDROXY-3-[(3-METHOXYBENZYL)AMINO]PROPYL}-5-[METHYL(METHYLSULFONYL)AMINO]-N-[(1R)-1-PHENYLETHYL]BENZENE-1,3-DICARBOXAMIDE'>BSD</scene><br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BSD:N-{(1S,2R)-1-BENZYL-2-HYDROXY-3-[(3-METHOXYBENZYL)AMINO]PROPYL}-5-[METHYL(METHYLSULFONYL)AMINO]-N-[(1R)-1-PHENYLETHYL]BENZENE-1,3-DICARBOXAMIDE'>BSD</scene></td></tr>
-<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1fkn|1fkn]], [[1py1|1py1]], [[1tqf|1tqf]], [[1ujj|1ujj]], [[1ujk|1ujk]], [[1xn2|1xn2]], [[1xn3|1xn3]], [[1ym2|1ym2]], [[2b8l|2b8l]], [[2b8v|2b8v]], [[2va5|2va5]], [[2va6|2va6]], [[2va7|2va7]], [[2vie|2vie]], [[2vij|2vij]], [[2viy|2viy]], [[2vj7|2vj7]], [[1m4h|1m4h]], [[1sgz|1sgz]], [[1w50|1w50]], [[1w51|1w51]], [[1xs7|1xs7]], [[1ym4|1ym4]], [[2viz|2viz]], [[2vj6|2vj6]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1fkn|1fkn]], [[1py1|1py1]], [[1tqf|1tqf]], [[1ujj|1ujj]], [[1ujk|1ujk]], [[1xn2|1xn2]], [[1xn3|1xn3]], [[1ym2|1ym2]], [[2b8l|2b8l]], [[2b8v|2b8v]], [[2va5|2va5]], [[2va6|2va6]], [[2va7|2va7]], [[2vie|2vie]], [[2vij|2vij]], [[2viy|2viy]], [[2vj7|2vj7]], [[1m4h|1m4h]], [[1sgz|1sgz]], [[1w50|1w50]], [[1w51|1w51]], [[1xs7|1xs7]], [[1ym4|1ym4]], [[2viz|2viz]], [[2vj6|2vj6]]</td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2vkm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vkm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2vkm RCSB], [http://www.ebi.ac.uk/pdbsum/2vkm 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=2vkm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vkm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2vkm RCSB], [http://www.ebi.ac.uk/pdbsum/2vkm PDBsum]</span></td></tr>
-<table>
+</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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 33: / Line 35: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Ghosh, A K.]]
+[[Category: Ghosh, A K]]
-[[Category: Hong, L.]]
+[[Category: Hong, L]]
-[[Category: Tang, J.]]
+[[Category: Tang, J]]
 [[Category: A-beta]]
 [[Category: Alzheimer]]

2vkm

From Proteopedia

Revision as of 20:40, 24 December 2014

CRYSTAL STRUCTURE OF GRL-8234 BOUND TO BACE (BETA-SECRETASE)

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox