OCA at 07:09, 15 February 2018

2018-02-15T07:09:02Z

← Older revision		Revision as of 07:09, 15 February 2018
Line 3:		Line 3:
	<StructureSection load='6eor' size='340' side='right' caption='[[6eor]], [[Resolution\|resolution]] 2.90Å' scene=''>		<StructureSection load='6eor' size='340' side='right' caption='[[6eor]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6eor]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EOR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EOR FirstGlance]. <br>		<table><tr><td colspan='2'>[[6eor]] is a 4 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=6EOR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EOR FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9XH:(2~{S})-2-azanyl-4-[4-[bis(4-fluorophenyl)methyl]piperazin-1-yl]-1-(1,3-dihydroisoindol-2-yl)butane-1,4-dione'>9XH</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9XH:(2~{S})-2-azanyl-4-[4-[bis(4-fluorophenyl)methyl]piperazin-1-yl]-1-(1,3-dihydroisoindol-2-yl)butane-1,4-dione'>9XH</scene></td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">DPP9, DPRP2 ([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/Dipeptidyl-peptidase_IV Dipeptidyl-peptidase IV], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.14.5 3.4.14.5] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dipeptidyl-peptidase_IV Dipeptidyl-peptidase IV], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.14.5 3.4.14.5] </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=6eor FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eor OCA], [http://pdbe.org/6eor PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6eor RCSB], [http://www.ebi.ac.uk/pdbsum/6eor PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6eor ProSAT]</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=6eor FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eor OCA], [http://pdbe.org/6eor PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6eor RCSB], [http://www.ebi.ac.uk/pdbsum/6eor PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6eor ProSAT]</span></td></tr>
Line 12:		Line 13:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/DPP9_HUMAN DPP9_HUMAN]] Dipeptidyl peptidase that cleaves off N-terminal dipeptides from proteins having a Pro or Ala residue at position 2.		[[http://www.uniprot.org/uniprot/DPP9_HUMAN DPP9_HUMAN]] Dipeptidyl peptidase that cleaves off N-terminal dipeptides from proteins having a Pro or Ala residue at position 2.
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Dipeptidyl peptidases 8 and 9 are intracellular N-terminal dipeptidyl peptidases (preferentially postproline) associated with pathophysiological roles in immune response and cancer biology. While the DPP family member DPP4 is extensively characterized in molecular terms as a validated therapeutic target of type II diabetes, experimental 3D structures and ligand-/substrate-binding modes of DPP8 and DPP9 have not been reported. In this study we describe crystal and molecular structures of human DPP8 (2.5 A) and DPP9 (3.0 A) unliganded and complexed with a noncanonical substrate and a small molecule inhibitor, respectively. Similar to DPP4, DPP8 and DPP9 molecules consist of one beta-propeller and alpha/beta hydrolase domain, forming a functional homodimer. However, they differ extensively in the ligand binding site structure. In intriguing contrast to DPP4, where liganded and unliganded forms are closely similar, ligand binding to DPP8/9 induces an extensive rearrangement at the active site through a disorder-order transition of a 26-residue loop segment, which partially folds into an alpha-helix (R-helix), including R160/133, a key residue for substrate binding. As vestiges of this helix are also seen in one of the copies of the unliganded form, conformational selection may contributes to ligand binding. Molecular dynamics simulations support increased flexibility of the R-helix in the unliganded state. Consistently, enzyme kinetics assays reveal a cooperative allosteric mechanism. DPP8 and DPP9 are closely similar and display few opportunities for targeted ligand design. However, extensive differences from DPP4 provide multiple cues for specific inhibitor design and development of the DPP family members as therapeutic targets or antitargets.

			Structures and mechanism of dipeptidyl peptidases 8 and 9, important players in cellular homeostasis and cancer.,Ross B, Krapp S, Augustin M, Kierfersauer R, Arciniega M, Geiss-Friedlander R, Huber R Proc Natl Acad Sci U S A. 2018 Jan 30. pii: 1717565115. doi:, 10.1073/pnas.1717565115. PMID:29382749<ref>PMID:29382749</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 6eor" style="background-color:#fffaf0;"></div>
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Dipeptidyl-peptidase IV]]		[[Category: Dipeptidyl-peptidase IV]]
			[[Category: Human]]
	[[Category: Huber, R]]		[[Category: Huber, R]]
	[[Category: Ross, B R]]		[[Category: Ross, B R]]
	[[Category: Dpp9]]		[[Category: Dpp9]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]

OCA at 06:21, 7 February 2018

2018-02-07T06:21:36Z

← Older revision		Revision as of 06:21, 7 February 2018
Line 1:		Line 1:
	~~'''Unreleased structure'''~~

	~~The entry~~ 6eor is ~~ON HOLD until Paper Publication~~		==DPP9 - 1G244==
			<StructureSection load='6eor' size='340' side='right' caption='[[6eor]], [[Resolution\|resolution]] 2.90Å' scene=''>
	~~Authors~~: ~~Ross~~, B.R., ~~Huber~~, R.		== Structural highlights ==
			<table><tr><td colspan='2'>[[6eor]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EOR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EOR FirstGlance]. <br>
	~~Description~~: ~~DPP9 -1G244~~		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9XH:(2~{S})-2-azanyl-4-[4-[bis(4-fluorophenyl)methyl]piperazin-1-yl]-1-(1,3-dihydroisoindol-2-yl)butane-1,4-dione'>9XH</scene></td></tr>
	[[~~Category~~: ~~Unreleased Structures~~]]		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dipeptidyl-peptidase_IV Dipeptidyl-peptidase IV], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.14.5 3.4.14.5] </span></td></tr>
	[[Category: ~~Ross, B.R~~]]		<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=6eor FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eor OCA], [http://pdbe.org/6eor PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6eor RCSB], [http://www.ebi.ac.uk/pdbsum/6eor PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6eor ProSAT]</span></td></tr>
			</table>
			== Disease ==
			[[http://www.uniprot.org/uniprot/DPP9_HUMAN DPP9_HUMAN]] Idiopathic pulmonary fibrosis.
			== Function ==
			[[http://www.uniprot.org/uniprot/DPP9_HUMAN DPP9_HUMAN]] Dipeptidyl peptidase that cleaves off N-terminal dipeptides from proteins having a Pro or Ala residue at position 2.
			__TOC__
			</StructureSection>
			[[Category: Dipeptidyl-peptidase IV]]
	[[Category: Huber, R]]		[[Category: Huber, R]]
			[[Category: Ross, B R]]
			[[Category: Dpp9]]
			[[Category: Hydrolase]]

OCA: Protected "6eor" [edit=sysop:move=sysop]

2017-11-29T05:11:10Z

Protected "6eor" [edit=sysop:move=sysop]

← Older revision	Revision as of 05:11, 29 November 2017
(No difference)

OCA: New page: '''Unreleased structure''' The entry 6eor is ON HOLD until Paper Publication Authors: Ross, B.R., Huber, R. Description: DPP9 -1G244 Category: Unreleased Structures [[Category: Ros...

2017-11-29T05:11:09Z

New page: '''Unreleased structure''' The entry 6eor is ON HOLD until Paper Publication Authors: Ross, B.R., Huber, R. Description: DPP9 -1G244 Category: Unreleased Structures [[Category: Ros...

New page

'''Unreleased structure'''

The entry 6eor is ON HOLD until Paper Publication

Authors: Ross, B.R., Huber, R.

Description: DPP9 -1G244
[[Category: Unreleased Structures]]
[[Category: Ross, B.R]]
[[Category: Huber, R]]

6eor - Revision history

OCA at 07:09, 15 February 2018

OCA at 06:21, 7 February 2018

OCA: Protected "6eor" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 6eor is ON HOLD until Paper Publication Authors: Ross, B.R., Huber, R. Description: DPP9 -1G244 Category: Unreleased Structures [[Category: Ros...