Multidomain subunits

All known eight-stranded a/p-barrel domains have enzymatic functions that include isomerization of small sugar molecules, oxidation by flavin coenzymes, phosphate transfer, and degradation of sugar polymers. In some of these enzymes the barrel domain comprises the whole subunit of the protein in others the polypeptide chain is longer and forms several additional domains. An enzymatic function in these multidomain subunits, however, is always associated with the barrel domain. 

A final crucial issue is the structure of the polyketide assembly lines. The aromatic PKSs apparently require association of their various subunits for proper functioning. In the absence of the appropriate PKS multidomain architecture, synthesis is generally inefficient and results in truncated metabolites that are subject to variable amounts of spontaneous chemistry [8,10,26], It remains unclear what minimum complement of activities is required to achieve the natural PKS products formed in vivo. A consensus is growing, however, that chain length control... 

Oligomeric states of similarly folded subunits can be very disparate in architecture through evolution and have implications in terms of functions as it has been well exemplified with the hemoglobin family (Royer et al. 2005). The gain of modularity expected by switching from a single domain to multidomains proteins and then to supramolecular assemblies, the fact that components of stable complexes are more conserved than transient ones as well as the fact that essential proteins tend to be subunit of complexes have been discussed from the point of view of evolution (Pereira-Leal et al. 2006 Bomberg-Bauer et al. 2005). 

HIV-1 PR cleaves the multidomain protein encoded by the virus genome to yield separated structural proteins. Structure-based drug-design studies have shown that in the substrate-cleavage site - two Asp-Thr-Gly loops at the subunit-subunit interface (Fig. 5a) - the almost coplanar conformation of the catalytic Asp dyad is crucial for enzymatic function and for the binding of both substrate and inhibitors [88-90]. 

The individual modules of polyketide synthases (PKSs) and of NRPSs represent another example of modularity. An electrophile and a nucleophile are covalently attached to two different subunits of a multidomain enzyme. The selectivity for the electrophile resides in the domain catalyzing bond formation between two substrates and the selectivity for the nucleophile is controlled by a transfer domain which attaches the nucleophile onto a carrier domain. ... 

Protein tyrosine phosphatases. Phosphoprotein phosphatases are integral components of the signahng systems operated by protein kinases (Sun and Tonks, 1994). Cloning data show the protein tyrosine phosphatases (PTPs) to be a family of multidomain proteins having exceptional diversity. They can be broadly divided into two groups, the transmembrane or receptor-like PTPs and the cytosolic PTPs. None of these are related to the serine-threonine specific phosphatases. This is in contrast to the protein kinases (Seer-Thr and Tyr specific), which share a common ancestry. Unlike the Ser-Thr phosphatases, in which substrate specificity is determined by associated targeting subunits, the Tyr phosphatases are all monomeric enzymes. 

The multisubunits enzyme is encoded by the nuclear DNA, with the exception of the j8-subunit of carboxyltransferase that is encoded by a chloroplastic gene [11]. In grasses, the chloroplastic multidomain ACC is encoded by a nuclear gene, which is distinct from that coding for the cytosolic multidomain ACC. 

An extension of the concept of allostery has been proposed i.e., an interdomain transmission in multidomain protein. It has been accepted that in complemented elastase, the interactions between domains are not strong enough (compared with the native enzyme) to ensure allosteric transmission and amplification. The complemented enzyme behaves as a desensitized enzyme and therefore has only a weak activity. This extension is consistent with all other similarities between domains in multidomain proteins and subunits in oligomeric enzymes (Ghelis and Yon, 1979). 

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