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1sgz

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Revision as of 11:24, 24 December 2020

Crystal Structure of Unbound Beta-Secretase Catalytic Domain.

Structural highlights

1sgz is a 4 chain structure with sequence from Human. The July 2009 RCSB PDB Molecule of the Month feature on beta-Secretase by David Goodsell is 10.2210/rcsb_pdb/mom_2009_7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1fkn, 1m4h
Gene:	BACE, BACE1 (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

The three-dimensional structure of unbound human memapsin 2 (beta-secretase) protease domain determined at 2.0-A resolution has revealed a new position of the flap region, which appears to be locked in an "open" position. While the structure outside of the flap is essentially the same as the structure of memapsin 2 bound to an inhibitor, the flap positions are 4.5 A different at the tips. The open position of the flap in the current structure is stabilized by two newly formed intraflap hydrogen bonds and anchored by a new hydrogen bond involving the side chain of Tyr 71 (Tyr 75 in pepsin numbering) in a novel orientation. In molecular modeling experiments, the opening of the flap, 6.5 A at the narrowest point, permits entrance of substrates into the cleft. The narrowest point of the opening may function to discriminate among substrates based on sequence and shape. The observed flap opening may also serve as a model for the flap movement in the catalytic mechanism of eukaryotic aspartic proteases and provide insight for the side-chain selection in the design of memapsin 2 inhibitors.

Flap position of free memapsin 2 (beta-secretase), a model for flap opening in aspartic protease catalysis.,Hong L, Tang J Biochemistry. 2004 Apr 27;43(16):4689-95. PMID:15096037^[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
↑ Hong L, Tang J. Flap position of free memapsin 2 (beta-secretase), a model for flap opening in aspartic protease catalysis. Biochemistry. 2004 Apr 27;43(16):4689-95. PMID:15096037 doi:10.1021/bi0498252

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/1sgz"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of Unbound Beta-Secretase Catalytic Domain.==
-<StructureSection load='1sgz' size='340' side='right' caption='[[1sgz]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+<StructureSection load='1sgz' size='340' side='right'caption='[[1sgz]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1sgz]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. The July 2009 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''beta-Secretase''  by David Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2009_7 10.2210/rcsb_pdb/mom_2009_7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SGZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1SGZ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1sgz]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. The July 2009 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''beta-Secretase''  by David Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2009_7 10.2210/rcsb_pdb/mom_2009_7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SGZ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1SGZ FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1fkn|1fkn]], [[1m4h|1m4h]]</td></tr>
+</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1fkn|1fkn]], [[1m4h|1m4h]]</div></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BACE, BACE1 ([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=1sgz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sgz OCA], [http://pdbe.org/1sgz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1sgz RCSB], [http://www.ebi.ac.uk/pdbsum/1sgz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1sgz ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1sgz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sgz OCA], [http://pdbe.org/1sgz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1sgz RCSB], [http://www.ebi.ac.uk/pdbsum/1sgz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1sgz ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 32: / Line 32: @@
 ==See Also==
-*[[Beta secretase|Beta secretase]]
+*[[Beta secretase 3D structures|Beta secretase 3D structures]]
 == References ==
 <references/>
@@ Line 38: / Line 38: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Memapsin 2]]
 [[Category: RCSB PDB Molecule of the Month]]

1sgz

From Proteopedia

Revision as of 11:24, 24 December 2020

Crystal Structure of Unbound Beta-Secretase Catalytic Domain.

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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