1dbb: Difference between revisions

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THREE-DIMENSIONAL STRUCTURE OF AN ANTI-STEROID FAB' AND PROGESTERONE-FAB' COMPLEX

OverviewOverview

The monoclonal anti-progesterone antibody DB3 binds progesterone with nanomolar affinity (Ka approximately 10(9) M-1), suggesting high specificity. However, DB3 also cross-reacts with similar affinity with a subgroup of structurally distinct, progesterone-like steroids. Crystals of the unliganded Fab' and various steroid-Fab' complexes are isomorphous and belong to the hexagonal space group, P6(4)22, with unit cell dimensions of a = b = 135 A, c = 124 A. Structures of free and progesterone-bound Fab' have been determined by X-ray crystallography at 2.7 A resolution using molecular replacement techniques. Progesterone is bound in a hydrophobic pocket formed mainly by the interaction of three complementarity determining regions L1, H2 and H3. The orientation of the ligand in the binding site was aided by both crystallographic and biochemical analyses of substituted steroids. The indole side-chain of TrpH100 of the DB3 has two different conformations, inter-converting "open" and "closed" forms of the antibody combining site. The TrpH100 indole thus appears to be acting as an antibody-derived surrogate ligand for its own hydrophobic binding pocket. These structures provide the first atomic view of how a steroid interacts with a protein and offer a structural explanation for the restriction of the anti-progesterone response to the VGAM3.8 family of VH genes.

About this StructureAbout this Structure

1DBB is a Protein complex structure of sequences from [1] with as ligand. Full crystallographic information is available from OCA.

ReferenceReference

Three-dimensional structure of an anti-steroid Fab' and progesterone-Fab' complex., Arevalo JH, Stura EA, Taussig MJ, Wilson IA, J Mol Biol. 1993 May 5;231(1):103-18. PMID:8496956

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 ==Overview==
-The monoclonal anti-progesterone antibody DB3 binds progesterone with, nanomolar affinity (Ka approximately 10(9) M-1), suggesting high, specificity. However, DB3 also cross-reacts with similar affinity with a, subgroup of structurally distinct, progesterone-like steroids. Crystals of, the unliganded Fab' and various steroid-Fab' complexes are isomorphous and, belong to the hexagonal space group, P6(4)22, with unit cell dimensions of, a = b = 135 A, c = 124 A. Structures of free and progesterone-bound Fab', have been determined by X-ray crystallography at 2.7 A resolution using, molecular replacement techniques. Progesterone is bound in a hydrophobic, pocket formed mainly by the interaction of three complementarity, determining regions L1, H2 and H3. The orientation of the ligand in the, binding site was aided by both crystallographic and biochemical analyses, of substituted steroids. The indole side-chain of TrpH100 of the DB3 has, two different conformations, inter-converting "open" and "closed" forms of, the antibody combining site. The TrpH100 indole thus appears to be acting, as an antibody-derived surrogate ligand for its own hydrophobic binding, pocket. These structures provide the first atomic view of how a steroid, interacts with a protein and offer a structural explanation for the, restriction of the anti-progesterone response to the VGAM3.8 family of VH, genes.
+The monoclonal anti-progesterone antibody DB3 binds progesterone with nanomolar affinity (Ka approximately 10(9) M-1), suggesting high specificity. However, DB3 also cross-reacts with similar affinity with a subgroup of structurally distinct, progesterone-like steroids. Crystals of the unliganded Fab' and various steroid-Fab' complexes are isomorphous and belong to the hexagonal space group, P6(4)22, with unit cell dimensions of a = b = 135 A, c = 124 A. Structures of free and progesterone-bound Fab' have been determined by X-ray crystallography at 2.7 A resolution using molecular replacement techniques. Progesterone is bound in a hydrophobic pocket formed mainly by the interaction of three complementarity determining regions L1, H2 and H3. The orientation of the ligand in the binding site was aided by both crystallographic and biochemical analyses of substituted steroids. The indole side-chain of TrpH100 of the DB3 has two different conformations, inter-converting "open" and "closed" forms of the antibody combining site. The TrpH100 indole thus appears to be acting as an antibody-derived surrogate ligand for its own hydrophobic binding pocket. These structures provide the first atomic view of how a steroid interacts with a protein and offer a structural explanation for the restriction of the anti-progesterone response to the VGAM3.8 family of VH genes.
 ==About this Structure==
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 Three-dimensional structure of an anti-steroid Fab' and progesterone-Fab' complex., Arevalo JH, Stura EA, Taussig MJ, Wilson IA, J Mol Biol. 1993 May 5;231(1):103-18. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=8496956 8496956]
 [[Category: Protein complex]]
-[[Category: Arevalo, J.H.]]
+[[Category: Arevalo, J H.]]
-[[Category: Wilson, I.A.]]
+[[Category: Wilson, I A.]]
 [[Category: STR]]
 [[Category: immunoglobulin]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 15:39:09 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:14:54 2008''