Evolution of shape complementarity and catalytic efficiency from a primordial antibody template.
The crystal structure of an efficient Diels-Alder antibody catalyst at 1.9 angstrom resolution reveals almost perfect shape complementarity with its transition state analog. Comparison with highly related progesterone and Diels-Alderase antibodies that arose from the same primordial germ line template shows the relatively subtle mutational steps that were able to evolve both structural complementarity and catalytic efficiency.
Xu
J
J
Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Deng
Q
Q
Chen
J
J
Houk
K N
KN
Bartek
J
J
Hilvert
D
D
Wilson
I A
IA
D017151:Antibodies, Catalytic / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001666:Binding Sites, Antibody; D002384:Catalysis; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D018360:Crystallography, X-Ray; D019143:Evolution, Molecular; D006241:Haptens / Q000737:chemistry / Q000378:metabolism; D006860:Hydrogen Bonding; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D009154:Mutation; D011374:Progesterone / Q000276:immunology; D011487:Protein Conformation; D012995:Solubility; D013696:Temperature; D013698:Templates, Genetic
D017151:Antibodies, Catalytic; D006241:Haptens; D007140:Immunoglobulin Fab Fragments; D008024:Ligands; D011374:Progesterone