1tqf

From Proteopedia

(Difference between revisions)

Revision as of 08:24, 21 March 2018

Crystal structure of human Beta secretase complexed with inhibitor

Structural highlights

1tqf 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 small molecule nonpeptide inhibitor of beta-secretase has been developed, and its binding has been defined through crystallographic determination of the enzyme-inhibitor complex. The molecule is shown to bind to the catalytic aspartate residues in an unprecedented manner in the field of aspartyl protease inhibition. Additionally, the complex reveals a heretofore unknown S(3) subpocket that is created by the inhibitor. This structure has served an important role in the design of newer beta-secretase inhibitors.

Identification of a small molecule nonpeptide active site beta-secretase inhibitor that displays a nontraditional binding mode for aspartyl proteases.,Coburn CA, Stachel SJ, Li YM, Rush DM, Steele TG, Chen-Dodson E, Holloway MK, Xu M, Huang Q, Lai MT, DiMuzio J, Crouthamel MC, Shi XP, Sardana V, Chen Z, Munshi S, Kuo L, Makara GM, Annis DA, Tadikonda PK, Nash HM, Vacca JP, Wang T J Med Chem. 2004 Dec 2;47(25):6117-9. PMID:15566281^[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
↑ Coburn CA, Stachel SJ, Li YM, Rush DM, Steele TG, Chen-Dodson E, Holloway MK, Xu M, Huang Q, Lai MT, DiMuzio J, Crouthamel MC, Shi XP, Sardana V, Chen Z, Munshi S, Kuo L, Makara GM, Annis DA, Tadikonda PK, Nash HM, Vacca JP, Wang T. Identification of a small molecule nonpeptide active site beta-secretase inhibitor that displays a nontraditional binding mode for aspartyl proteases. J Med Chem. 2004 Dec 2;47(25):6117-9. PMID:15566281 doi:10.1021/jm049388p

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/1tqf"

@@ Line 1: / Line 1: @@
 ==Crystal structure of human Beta secretase complexed with inhibitor==
 <StructureSection load='1tqf' size='340' side='right' caption='[[1tqf]], [[Resolution|resolution]] 1.80&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=1tqf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tqf OCA], [http://pdbe.org/1tqf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1tqf RCSB], [http://www.ebi.ac.uk/pdbsum/1tqf 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=1tqf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tqf OCA], [http://pdbe.org/1tqf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1tqf RCSB], [http://www.ebi.ac.uk/pdbsum/1tqf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1tqf 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/tq/1tqf_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/tq/1tqf_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

1tqf

From Proteopedia

Revision as of 08:24, 21 March 2018

Crystal structure of human Beta secretase complexed with inhibitor

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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