title: Secondary interactions involving zinc-bound ligands: roles in structural stabilization and macromolecular interactions.
abstract: A large number of proteins contain bound zinc ions. These zinc ions are frequently coordinated by a combination of histidine and cysteine residues. In addition to atoms that coordinate directly to the zinc ions, these side chains have groups that can donate or accept hydrogen bonds from other groups. These secondary interactions can help stabilize the zinc-binding sites, can contribute to protein folding and stability, and, on occasion, can participate in interactions with other macromolecules. Five examples of these secondary interactions are discussed: carbonic anhydrase (where secondary interactions involving histidine residues stabilize the zinc-binding site thermodynamically and kinetically), retroviral nucleocapsid proteins and TRAF proteins (where cysteinate sulfur to peptide NH hydrogen bonds contribute to the structural relationships between adjacent domains), and nucleic acid binding proteins, Zif268 and TIS11 where secondary interactions participate in protein-nucleic acid interactions.
authors.affiliation: Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases/NIH, Bethesda, MD 20892, United States.
authors.forename: Frances
authors.initials: F
authors.lastname: Namuswe
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Berg
mesh_terms: D002256:Carbonic Anhydrases / Q000737:chemistry / Q000378:metabolism; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism; D051766:Early Growth Response Protein 1 / Q000737:chemistry / Q000378:metabolism; D006639:Histidine / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D008024:Ligands; D008667:Metalloproteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D019590:Nucleocapsid Proteins / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D048029:TNF Receptor-Associated Factor 6 / Q000737:chemistry / Q000378:metabolism; D051816:Tristetraprolin / Q000737:chemistry / Q000378:metabolism; D015032:Zinc / Q000737:chemistry* / Q000378:metabolism
chemical_list: C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D008024:Ligands; D008667:Metalloproteins; D019590:Nucleocapsid Proteins; D048029:TNF Receptor-Associated Factor 6; D051816:Tristetraprolin; C497552:ZFP36 protein, human; D006639:Histidine; D002256:Carbonic Anhydrases; D015032:Zinc; D003545:Cysteine