This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


1flz

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:1flz.jpg|left|200px]]
+
{{Seed}}
 +
[[Image:1flz.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_1flz| PDB=1flz | SCENE= }}
{{STRUCTURE_1flz| PDB=1flz | SCENE= }}
-
'''URACIL DNA GLYCOSYLASE WITH UAAP'''
+
===URACIL DNA GLYCOSYLASE WITH UAAP===
-
==Overview==
+
<!--
-
The DNA repair enzyme uracil DNA glycosylase (UDG) pinches the phosphodiester backbone of damaged DNA using the hydroxyl side chains of a conserved trio of serine residues, resulting in flipping of the deoxyuridine from the DNA helix into the enzyme active site. We have investigated the energetic role of these serine-phosphodiester interactions using the complementary approaches of crystallography, directed mutagenesis, and stereospecific phosphorothioate substitutions. A new crystal structure of UDG bound to 5'-HO-dUAAp-3' (which lacks the 5' phosphodiester group that interacts with the Ser88 pinching finger) shows that the glycosidic bond of dU has been cleaved, and that the enzyme has undergone the same specific clamping motion that brings key active site groups into position as previously observed in the structures of human UDG bound to large duplex DNA substrates. From this structure, it may be concluded that glycosidic bond cleavage and the induced fit conformational change in UDG can occur without the 5' pinching interaction. The S88A, S189A, and S192G "pinching" mutations exhibit 360-, 80-, and 21-fold damaging effects on k(cat)/K(m), respectively, while the S88A/S189A double mutant exhibits an 8200-fold damaging effect. A free energy analysis of the combined effects of nonbridging phosphorothioate substitution and mutation at these positions reveals the presence of a modest amount of strain energy between the compressed 5' and 3' phosphodiester groups flanking the bound uridine. Overall, these results indicate a role for these serine-phosphodiester interactions in uracil flipping and preorganization of the sugar ring into a reactive conformation. However, in contrast to a recent proposal [Parikh, S. S., et al. (2000) Proc Natl. Acad. Sci. 94, 5083], there is no evidence that conformational strain of the glycosidic bond induced by serine pinching plays a major role in the 10(12)-fold rate enhancement brought about by UDG.
+
The line below this paragraph, {{ABSTRACT_PUBMED_11027138}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 11027138 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_11027138}}
==About this Structure==
==About this Structure==
Line 34: Line 38:
[[Category: Glycosylase]]
[[Category: Glycosylase]]
[[Category: Hydrolase]]
[[Category: Hydrolase]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 16:29:07 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 03:27:55 2008''

Revision as of 00:27, 1 July 2008

Image:1flz.png

Template:STRUCTURE 1flz

URACIL DNA GLYCOSYLASE WITH UAAP

Template:ABSTRACT PUBMED 11027138

About this Structure

1FLZ is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.

Reference

Stressing-out DNA? The contribution of serine-phosphodiester interactions in catalysis by uracil DNA glycosylase., Werner RM, Jiang YL, Gordley RG, Jagadeesh GJ, Ladner JE, Xiao G, Tordova M, Gilliland GL, Stivers JT, Biochemistry. 2000 Oct 17;39(41):12585-94. PMID:11027138

Page seeded by OCA on Tue Jul 1 03:27:55 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1flz"
Personal tools