1orv: Difference between revisions
New page: left|200px<br /><applet load="1orv" size="450" color="white" frame="true" align="right" spinBox="true" caption="1orv, resolution 1.80Å" /> '''Crystal Structure of... |
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[[Image:1orv.jpg|left|200px]]<br /><applet load="1orv" size=" | [[Image:1orv.jpg|left|200px]]<br /><applet load="1orv" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1orv, resolution 1.80Å" /> | caption="1orv, resolution 1.80Å" /> | ||
'''Crystal Structure of Porcine Dipeptidyl Peptidase IV (CD26)'''<br /> | '''Crystal Structure of Porcine Dipeptidyl Peptidase IV (CD26)'''<br /> | ||
==Overview== | ==Overview== | ||
The membrane-bound glycoprotein dipeptidyl peptidase IV (DP IV, CD26) is a | The membrane-bound glycoprotein dipeptidyl peptidase IV (DP IV, CD26) is a unique multifunctional protein, acting as receptor, binding and proteolytic molecule. We have determined the sequence and 1.8 A crystal structure of native DP IV prepared from porcine kidney. The crystal structure reveals a 2-2-2 symmetric tetrameric assembly which depends on the natively glycosylated beta-propeller blade IV. The crystal structure indicates that tetramerization of DP IV is a key mechanism to regulate its interaction with other components. Each subunit comprises two structural domains, the N-terminal eight-bladed beta-propeller with open Velcro topology and the C-terminal alpha/beta-hydrolase domain. Analogy with the structurally related POP and tricorn protease suggests that substrates access the buried active site through the beta-propeller tunnel while products leave the active site through a separate side exit. A dipeptide mimicking inhibitor complexed to the active site discloses key determinants for substrate recognition, including a Glu-Glu motif that distinguishes DP IV as an aminopeptidase and an oxyanion trap that binds and activates the P(2)-carbonyl oxygen necessary for efficient postproline cleavage. We discuss active and nonactive site-directed inhibition strategies of this pharmaceutical target protein. | ||
==About this Structure== | ==About this Structure== | ||
1ORV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with NAG and SO4 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | 1ORV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with <scene name='pdbligand=NAG:'>NAG</scene> and <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ORV OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Bode, W.]] | [[Category: Bode, W.]] | ||
[[Category: Brandstetter, H.]] | [[Category: Brandstetter, H.]] | ||
[[Category: Demuth, H | [[Category: Demuth, H U.]] | ||
[[Category: Engel, M.]] | [[Category: Engel, M.]] | ||
[[Category: Heiser, U.]] | [[Category: Heiser, U.]] | ||
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[[Category: substrate channeling]] | [[Category: substrate channeling]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:20:53 2008'' | ||
Revision as of 15:20, 21 February 2008
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Crystal Structure of Porcine Dipeptidyl Peptidase IV (CD26)
OverviewOverview
The membrane-bound glycoprotein dipeptidyl peptidase IV (DP IV, CD26) is a unique multifunctional protein, acting as receptor, binding and proteolytic molecule. We have determined the sequence and 1.8 A crystal structure of native DP IV prepared from porcine kidney. The crystal structure reveals a 2-2-2 symmetric tetrameric assembly which depends on the natively glycosylated beta-propeller blade IV. The crystal structure indicates that tetramerization of DP IV is a key mechanism to regulate its interaction with other components. Each subunit comprises two structural domains, the N-terminal eight-bladed beta-propeller with open Velcro topology and the C-terminal alpha/beta-hydrolase domain. Analogy with the structurally related POP and tricorn protease suggests that substrates access the buried active site through the beta-propeller tunnel while products leave the active site through a separate side exit. A dipeptide mimicking inhibitor complexed to the active site discloses key determinants for substrate recognition, including a Glu-Glu motif that distinguishes DP IV as an aminopeptidase and an oxyanion trap that binds and activates the P(2)-carbonyl oxygen necessary for efficient postproline cleavage. We discuss active and nonactive site-directed inhibition strategies of this pharmaceutical target protein.
About this StructureAbout this Structure
1ORV is a Single protein structure of sequence from Sus scrofa with and as ligands. Active as Dipeptidyl-peptidase IV, with EC number 3.4.14.5 Full crystallographic information is available from OCA.
ReferenceReference
The crystal structure of dipeptidyl peptidase IV (CD26) reveals its functional regulation and enzymatic mechanism., Engel M, Hoffmann T, Wagner L, Wermann M, Heiser U, Kiefersauer R, Huber R, Bode W, Demuth HU, Brandstetter H, Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5063-8. Epub 2003 Apr 10. PMID:12690074
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