The atomic resolution structure of human aldose reductase reveals that rearrangement of a bound ligand allows the opening of the safety-belt loop.
The crystal structure of human aldose reductase in complex with citrate has been determined to a resolution of 0.82 A. The difference electron density for H atoms unequivocally shows that the cofactor is in the oxidized state corresponding to the situation after the catalytic event has occurred. A citrate molecule bound to the active site has been modelled in two different conformations. These two conformations correlate with a fully closed and a partially open conformation of the so-called safety-belt loop (Gly213-Ser226). The open conformation is observed for the first time with the cofactor bound to the protein and may be related to the initial phase of the opening of the safety belt. The structure suggests that after the catalytic event, a rearrangement of a bound ligand can trigger the opening of the safety-belt loop, thus initiating the release of the oxidized cofactor.
Biadene
Marianna
M
Lehrstuhl für Strukturchemie, Georg-August Universität, Tammanstrasse 4, D-37077 Göttingen, Germany.
Hazemann
Isabelle
I
Cousido
Alexandra
A
Ginell
Steve
S
Joachimiak
Andrzej
A
Sheldrick
George M
GM
Podjarny
Alberto
A
Schneider
Thomas R
TR
D000449:Aldehyde Reductase / Q000737:chemistry* / Q000235:genetics; D020134:Catalytic Domain; D019343:Citric Acid / Q000737:chemistry; D018360:Crystallography, X-Ray; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D055672:Static Electricity
D008024:Ligands; D011994:Recombinant Proteins; D019343:Citric Acid; C484670:AKR1B1 protein, human; D000449:Aldehyde Reductase