Nature Structural Biology pp 215 - 220 and pp 221 - 225

If you visit the nursery in a hospital, you may see babies under fluorescent lamps — these babies are undergoing treatment for jaundice, a condition caused by the abnormally high level of bilirubins in the bloodstream. Bilirubins can be neurotoxic, and accumulation of this compound in an infant's brain could cause irreversible damage.

Bilirubins are the breakdown product of heme — the oxygen-binding factor of hemoglobin — released from red blood cells that have been destroyed. However, they are not waste products that are completely bad for us. In fact, bilirubins are potent antioxidants made by the human body. Thus, the molecular details of how they are converted from heme are important for understanding how bilirubin production is regulated to benefit rather than harm us.

Heme is converted into bilirubins in two steps: it is first cleaved to produce unstable intermediates, biliverdins; these intermediates are then further processed to bilirubins by enzymes called biliverdin reductases. To understand how these enzymes convert biliverdins into bilirubins, Miquel Coll of the Institut de Biologia Molecular de Barcelona, Spain, and his colleagues at Trinity College, Ireland, as well as Akihiro Kikuchi and coworkers at the RIKEN Harima Institute, Japan, have determined the crystal structures of two different biliverdin reductases. These structures provide a wealth of information about the molecular details of bilirubin production.

Antony McDonagh at the University of California San Francisco discusses these findings in an associated News and Views.

Nature Structural Biology pp 203 - 206

The central dogma holds that DNA gets copied into RNA that is then translated into protein. In the first step, the DNA is transcribed into messenger RNA (mRNA). This mRNA copy is then translated into protein. The mRNA is read in triplets (codons) that code for specific amino acids by transfer RNAs (tRNAs). Each tRNA binds an amino acid at one end and the codon of the mRNA at the other end via its anticodon. Thus, tRNAs act as adaptors to place particular amino acids in a particular order as coded for by the mRNA. Each tRNA also has a specific charger protein; this protein can only bind to that particular tRNA and attach the correct amino acid. These charger proteins are called aminoacyl tRNA synthetases. The fidelity of the genetic code is ensured by these enzymes.

Given that there are 20 different amino acids there theoretically should be 20 different aminoacyl tRNA sythetases — one to charge each tRNA. While this is the case in many organisms, some archaea and bacteria are able to make do with less than 20. This is accomplished by having some aminoacyl tRNA synthetases do double duty. For example, the tRNA for glutamine (tRNA^Gln) is charged with glutamate by the synthetase for glutamate and the glutamate is subsequently converted to glutamine by the action of another enzyme. This less discriminating aminoacyl tRNA sythetase must be able to recognize the anticodon on both tRNA^Gln and tRNA^Glu.

How does each different aminoacyl tRNA synthetase recognize a particular anticodon on the tRNA and charge it with a specific amino acid? How do the less discriminating enzymes still maintain some specificity? To try to answer these questions, Shigeyuki Yokoyama and coworkers of the RIKEN Institute and the University of Tokyo in Japan solved the X-ray crystal structure of the sythetase for glutamate with its cognate tRNA (tRNA^Glu). They find that a single amino acid on the synthetase (Arg 358) is important for specifically recognizing the tRNA^Glu anticodon. When this amino acid is changed to another, the aminoacyl tRNA sythetase cannot discriminate between the anticodons for tRNA^Glu and tRNA^Glu. This finding has interesting evolutionary implications for how a discriminating enzyme could have evolved from a less discriminating predecessor in just a single step. Christopher Francklyn discusses these results in an associated News and Views report.