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==antibody 64M-5 Fab in complex with dT(6-4)T==
==antibody 64M-5 Fab in complex with dT(6-4)T==
<StructureSection load='6idg' size='340' side='right' caption='[[6idg]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
<StructureSection load='6idg' size='340' side='right'caption='[[6idg]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6idg]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6IDG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6IDG FirstGlance]. <br>
<table><tr><td colspan='2'>[[6idg]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6IDG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6IDG FirstGlance]. <br>
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<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
DNA photoproducts with (6-4) pyrimidine-pyrimidone adducts formed by ultraviolet radiation have been implicated in mutagenesis and cancer. The crystal structure of double-stranded DNA containing the (6-4) photoproduct in complex with the anti-(6-4)-photoproduct antibody 64M-5 Fab was determined at 2.5 A resolution. The T(6-4)T segment and the 5'-side adjacent adenosine are flipped out of the duplex and are accommodated in the concave antigen-binding pocket composed of six complementarity-determining regions (CDRs). A loop comprised of CDR L1 residues is inserted between the flipped-out T(6-4)T segment and the complementary DNA. The separation of strands by the insertion of the loop facilitates extensive and specific recognition of the photoproduct. The DNA helices flanking the T(6-4)T segment are kinked by 87 degrees . The 64M-5 Fab recognizes the T(6-4)T segment dissociated from the complementary strand, indicating that the (6-4) photoproduct can be detected in double-stranded DNA as well as in single-stranded DNA using the 64M-5 antibody. The structure and recognition mode of the 64M-5 antibody were compared with those of the DNA (6-4) photolyase and nucleotide-excision repair protein DDB1-DDB2. These proteins have distinctive binding-site structures that are appropriate for their functions, and the flipping out of the photolesion and the kinking of the DNA are common to mutagenic (6-4) photoproducts recognized by proteins.
DNA photoproducts with (6-4) pyrimidine-pyrimidone adducts produced by ultraviolet light are mutagenic and carcinogenic. The crystal structures of the anti-(6-4) photoproduct antibody 64M-5 Fab and of its complex with dT(6-4)T were determined at 2.5 and 2.0 A resolution, respectively. A comparison between the dT(6-4)T-liganded and unliganded structures indicates that the side chain of His93L is greatly rotated and shifted on binding to dT(6-4)T, leading to the formation of an electrostatic interaction with the phosphate moiety of dT(6-4)T, which shows a remarkable induced fit. Based on a comparison of the dT(6-4)T-liganded structures of the 64M-5 and 64M-2 Fabs, the electrostatic interaction between the side chain of His93L in 64M-5 and the phosphate moiety of dT(6-4)T is lost for Leu93L in 64M-2, while Arg90L in 64M-5 instead of Gln90L in 64M-2 stabilizes the conformation of complementarity-determining region (CDR) L3. These differences contribute to the higher affinity of 64M-5 for dT(6-4)T compared with that of 64M-2.


Structure of a double-stranded DNA (6-4) photoproduct in complex with the 64M-5 antibody Fab.,Yokoyama H, Mizutani R, Satow Y Acta Crystallogr D Biol Crystallogr. 2013 Apr;69(Pt 4):504-12. doi:, 10.1107/S0907444912050007. Epub 2013 Mar 9. PMID:23519658<ref>PMID:23519658</ref>
Structures of the antibody 64M-5 Fab and its complex with dT(6-4)T indicate induced-fit and high-affinity mechanisms.,Yokoyama H, Mizutani R, Noguchi S, Hayashida N Acta Crystallogr F Struct Biol Commun. 2019 Feb 1;75(Pt 2):80-88. doi:, 10.1107/S2053230X18017661. Epub 2019 Jan 23. PMID:30713158<ref>PMID:30713158</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
</div>
<div class="pdbe-citations 6idg" style="background-color:#fffaf0;"></div>
<div class="pdbe-citations 6idg" style="background-color:#fffaf0;"></div>
==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Hayashida, N]]
[[Category: Hayashida, N]]

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