Structure
ADA exists in both small form (as a monomer) and large form (as a dimer-complex). In the monomer form, the enzyme is a single polypeptide chain, folded into eight strands of parallel α/β barrels, which surround a central deep pocket that is the active site. In addition to the eight central β-barrels and eight peripheral α-helices, ADA also contains five additional helices: residues 19-76 fold into three helices, located between β1 and α1 folds; and two antiparallel carboxy-terminal helices are located across the amino-terminal of the β-barrel.
The ADA active site contains a zinc ion, which is located in the deepest recess of the active site and coordinated by five atoms from His15, His17, His214, Asp295, and the substrate. Zinc is the only cofactor necessary for activity.
The substrate, adenosine, is stabilized and bound to the active site by nine hydrogen bonds. The carboxyl group of Glu217, roughly coplanar with the substrate purine ring, is in position to form a hydrogen bond with N1 of the substrate. The carboxyl group of Asp296, also coplanar with the substrate purine ring, forms hydrogen bond with N7 of the substrate. The NH group of Gly184 is in position to form a hydrogen bond with N3 of the substrate. Asp296 forms bonds both with the Zn2+ ion as well as with 6-OH of the substrate. His238 also hydrogen bonds to substrate 6-OH. The 3'-OH of the substrate ribose forms a hydrogen bond with Asp19, while the 5'-OH forms a hydrogen bond with His17. Two further hydrogen bonds are formed to water molecules, at the opening of the active site, by the 2'-OH and 3'-OH of the substrate.
Due to the recessing of the active inside the enzyme, the substrate once bound is almost completely sequestered from solvent. The surface exposure of the substrate to solvent when bound is 0.5% the surface exposure of the substrate in the free state.
Read more about this topic: Adenosine Deaminase
Famous quotes containing the word structure:
“A special feature of the structure of our book is the monstrous but perfectly organic part that eavesdropping plays in it.”
—Vladimir Nabokov (1899–1977)
“I’m a Sunday School teacher, and I’ve always known that the structure of law is founded on the Christian ethic that you shall love the Lord your God and your neighbor as yourself—a very high and perfect standard. We all know the fallibility of man, and the contentions in society, as described by Reinhold Niebuhr and many others, don’t permit us to achieve perfection.”
—Jimmy Carter (James Earl Carter, Jr.)
“Why does philosophy use concepts and why does faith use symbols if both try to express the same ultimate? The answer, of course, is that the relation to the ultimate is not the same in each case. The philosophical relation is in principle a detached description of the basic structure in which the ultimate manifests itself. The relation of faith is in principle an involved expression of concern about the meaning of the ultimate for the faithful.”
—Paul Tillich (1886–1965)