From Proteopedia
(Difference between revisions)
proteopedia linkproteopedia link
|
|
| Line 1: |
Line 1: |
| - | [[Image:2ugi.jpg|left|200px]] | + | {{Seed}} |
| | + | [[Image:2ugi.png|left|200px]] |
| | | | |
| | <!-- | | <!-- |
| Line 9: |
Line 10: |
| | {{STRUCTURE_2ugi| PDB=2ugi | SCENE= }} | | {{STRUCTURE_2ugi| PDB=2ugi | SCENE= }} |
| | | | |
| - | '''PROTEIN MIMICRY OF DNA FROM CRYSTAL STRUCTURES OF THE URACIL GLYCOSYLASE INHIBITOR PROTEIN AND ITS COMPLEX WITH ESCHERICHIA COLI URACIL-DNA GLYCOSYLASE'''
| + | ===PROTEIN MIMICRY OF DNA FROM CRYSTAL STRUCTURES OF THE URACIL GLYCOSYLASE INHIBITOR PROTEIN AND ITS COMPLEX WITH ESCHERICHIA COLI URACIL-DNA GLYCOSYLASE=== |
| | | | |
| | | | |
| - | ==Overview==
| + | <!-- |
| - | Uracil-DNA glycosylase (UDG), which is a critical enzyme in DNA base-excision repair that recognizes and removes uracil from DNA, is specifically and irreversably inhibited by the thermostable uracil-DNA glycosylase inhibitor protein (Ugi). A paradox for the highly specific Ugi inhibition of UDG is how Ugi can successfully mimic DNA backbone interactions for UDG without resulting in significant cross-reactivity with numerous other enzymes that possess DNA backbone binding affinity. High-resolution X-ray crystal structures of Ugi both free and in complex with wild-type and the functionally defective His187Asp mutant Escherichia coli UDGs reveal the detailed molecular basis for duplex DNA backbone mimicry by Ugi. The overall shape and charge distribution of Ugi most closely resembles a midpoint in a trajectory between B-form DNA and the kinked DNA observed in UDG:DNA product complexes. Thus, Ugi targets the mechanism of uracil flipping by UDG and appears to be a transition-state mimic for UDG-flipping of uracil nucleotides from DNA. Essentially all the exquisite shape, electrostatic and hydrophobic complementarity for the high-affinity UDG-Ugi interaction is pre-existing, except for a key flip of the Ugi Gln19 carbonyl group and Glu20 side-chain, which is triggered by the formation of the complex. Conformational changes between unbound Ugi and Ugi complexed with UDG involve the beta-zipper structural motif, which we have named for the reversible pairing observed between intramolecular beta-strands. A similar beta-zipper is observed in the conversion between the open and closed forms of UDG. The combination of extremely high levels of pre-existing structural complementarity to DNA binding features specific to UDG with key local conformational changes in Ugi resolves the UDG-Ugi paradox and suggests a potentially general structural solution to the formation of very high affinity DNA enzyme-inhibitor complexes that avoid cross- reactivity.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_10080896}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 10080896 is the PubMed ID number. |
| | + | --> |
| | + | {{ABSTRACT_PUBMED_10080896}} |
| | | | |
| | ==About this Structure== | | ==About this Structure== |
| Line 28: |
Line 32: |
| | [[Category: Protein inhibitor]] | | [[Category: Protein inhibitor]] |
| | [[Category: Protein mimicry of dna]] | | [[Category: Protein mimicry of dna]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 17:28:25 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 03:19:30 2008'' |
Revision as of 00:19, 28 July 2008
Template:STRUCTURE 2ugi
PROTEIN MIMICRY OF DNA FROM CRYSTAL STRUCTURES OF THE URACIL GLYCOSYLASE INHIBITOR PROTEIN AND ITS COMPLEX WITH ESCHERICHIA COLI URACIL-DNA GLYCOSYLASE
Template:ABSTRACT PUBMED 10080896
About this Structure
2UGI is a Single protein structure of sequence from Bacillus phage pbs2. Full crystallographic information is available from OCA.
Reference
Protein mimicry of DNA from crystal structures of the uracil-DNA glycosylase inhibitor protein and its complex with Escherichia coli uracil-DNA glycosylase., Putnam CD, Shroyer MJ, Lundquist AJ, Mol CD, Arvai AS, Mosbaugh DW, Tainer JA, J Mol Biol. 1999 Mar 26;287(2):331-46. PMID:10080896
Page seeded by OCA on Mon Jul 28 03:19:30 2008
