Domains closure

Fig. 4 Schematic section through the small ribosomal subunit of yeast (gray) exposing the decoding region. The model is based on structural work on the prokaryotic small ribosomal subunit. The homologous proteins of the E. coli decoding region are S4, S5, and S12 (Ogle et al. 2003). Movements within the small ribosomal subunit upon cognate tRNA binding (domain closure) are denoted by red arrows. Mutations in...

Szilagyi, A.N. Vas, M. Anion activation of 3-phosphoglycerate kinase requires domain closure. Biochemistry, 37, 8551-8563 (1998)... 

P. C. Engel, and D. W. Rice, Insights into the mechanism of domain closure and substrate sof glutamate dehydrogenase from Clostridium symbosium, J. Mol. Biol. 1999, 285, 875-885. 

During last decades the domains C-2 symmetry (the dyad rotation symmetry) of low-B palindrome was established in many enzymes (chymotrypsin, trypsin, aspartyl proteinases, HIV-1 protease, carboxypeptidase A, phospholipase A-2 ribonuclease, etc.) (Lumry, 2002 and references therein). It is proposed that the pair domain closure causes constrain of pretransition state complex that activates cleavage or formation of chemical bonds. Thus control of strong bonds by the cooperation of many matrix or knots bonds takes place. As an example, in the active site of carboxypeptidase A the zinc ion is attached to one of the catalytic domains by histidine 69 and glutamine 72 and connected by hystidine 196 to the second domain. Similar structures were found in the chymotrypsin and pepsin active sites where protons are driven under compression of the domains closure. 

Finally, the Asp ligand has been described as a trigger associated with domain closure (106). However, at a distance of 9 A from a metal ion bound to domain 2 it is hard to see how it could induce closure. Rather, it should be seen as a lock that holds the closed structure in place once the protein dynamics have brought the domains close together. 

Proper substrate binding allows for the hound (closed) state (EzS) to be in dynamic equilibrium with free substrate. Upon domain closure, catalytic reaction can occur to transform the bound state (EzS) to an energetically less stable state than the open state of the protein (F.zP) by altering the interactions between the protein and the bound molecule. Note that the upper limit on the rate of catalytic reaction should, therefore, be fixed by the rate of domain movements. Since the open state is more energetically favored, the product will desorb to return the enzyme to the open state. 

GJ. Schlauderer, K. Proba, and G.E. Schulz. 1996. Structure of a mutant adenylate kinase ligated with an ATP-analogue showing domain closure over ATP J. Mol. Biol. 256 223-221. (PubMed)... 

---