2bu2: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older editNewer edit →
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,329,905 edits
No edit summary
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,329,905 edits
No edit summary
Line 1: Line 1:
[[Image:2bu2.gif|left|200px]]
{{Seed}}
[[Image:2bu2.png|left|200px]]


<!--
<!--
Line 9: Line 10:
{{STRUCTURE_2bu2|  PDB=2bu2  |  SCENE=  }}  
{{STRUCTURE_2bu2|  PDB=2bu2  |  SCENE=  }}  


'''CRYSTAL STRUCTURES OF HUMAN PYRUVATE DEHYDROGENASE KINASE 2 CONTAINING PHYSIOLOGICAL AND SYNTHETIC LIGANDS'''
===CRYSTAL STRUCTURES OF HUMAN PYRUVATE DEHYDROGENASE KINASE 2 CONTAINING PHYSIOLOGICAL AND SYNTHETIC LIGANDS===




==Overview==
<!--  
Pyruvate dehydrogenase kinase (PDHK) regulates the activity of the pyruvate dehydrogenase multienzyme complex. PDHK inhibition provides a route for therapeutic intervention in diabetes and cardiovascular disorders. We report crystal structures of human PDHK isozyme 2 complexed with physiological and synthetic ligands. Several of the PDHK2 structures disclosed have C-terminal cross arms that span a large trough region between the N-terminal regulatory (R) domains of the PDHK2 dimers. The structures containing bound ATP and ADP demonstrate variation in the conformation of the active site lid, residues 316-321, which enclose the nucleotide beta and gamma phosphates at the active site in the C-terminal catalytic domain. We have identified three novel ligand binding sites located in the R domain of PDHK2. Dichloroacetate (DCA) binds at the pyruvate binding site in the center of the R domain, which together with ADP, induces significant changes at the active site. Nov3r and AZ12 inhibitors bind at the lipoamide binding site that is located at one end of the R domain. Pfz3 (an allosteric inhibitor) binds in an extended site at the other end of the R domain. We conclude that the N-terminal domain of PDHK has a key regulatory function and propose that the different inhibitor classes act by discrete mechanisms. The structures we describe provide insights that can be used for structure-based design of PDHK inhibitors.
The line below this paragraph, {{ABSTRACT_PUBMED_16401071}}, adds the Publication Abstract to the page
(as it appears on PubMed at http://www.pubmed.gov), where 16401071 is the PubMed ID number.
-->
{{ABSTRACT_PUBMED_16401071}}


==About this Structure==
==About this Structure==
Line 33: Line 37:
[[Category: Ghkl motif regulation]]
[[Category: Ghkl motif regulation]]
[[Category: Transferase]]
[[Category: Transferase]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 20:47:54 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 06:42:03 2008''

Revision as of 03:42, 29 July 2008

File:2bu2.png

Template:STRUCTURE 2bu2

CRYSTAL STRUCTURES OF HUMAN PYRUVATE DEHYDROGENASE KINASE 2 CONTAINING PHYSIOLOGICAL AND SYNTHETIC LIGANDS

Template:ABSTRACT PUBMED 16401071

About this Structure

2BU2 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Regulatory roles of the N-terminal domain based on crystal structures of human pyruvate dehydrogenase kinase 2 containing physiological and synthetic ligands., Knoechel TR, Tucker AD, Robinson CM, Phillips C, Taylor W, Bungay PJ, Kasten SA, Roche TE, Brown DG, Biochemistry. 2006 Jan 17;45(2):402-15. PMID:16401071

Page seeded by OCA on Tue Jul 29 06:42:03 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "https://proteopedia.org/index.php?title=2bu2&oldid=731399"