Tetrameric structures

The basic kinetic properties of this allosteric enzyme are clearly explained by combining Monod s theory and these structural results. The tetrameric enzyme exists in equilibrium between a catalytically active R state and an inactive T state. There is a difference in the tertiary structure of the subunits in these two states, which is closely linked to a difference in the quaternary structure of the molecule. The substrate F6P binds preferentially to the R state, thereby shifting the equilibrium to that state. Since the mechanism is concerted, binding of one F6P to the first subunit provides an additional three subunits in the R state, hence the cooperativity of F6P binding and catalysis. ATP binds to both states, so there is no shift in the equilibrium and hence there is no cooperativity of ATP binding. The inhibitor PEP preferentially binds to the effector binding site of molecules in the T state and as a result the equilibrium is shifted to the inactive state. By contrast the activator ADP preferentially binds to the effector site of molecules in the R state and as a result shifts the equilibrium to the R state with its four available, catalytically competent, active sites per molecule. 

The lac repressor monomer, a chain of 360 amino acids, associates into a functionally active homotetramer. It is the classic member of a large family of bacterial repressors with homologous amino acid sequences. PurR, which functions as the master regulator of purine biosynthesis, is another member of this family. In contrast to the lac repressor, the functional state of PurR is a dimer. The crystal structures of these two members of the Lac I family, in their complexes with DNA fragments, are known. The structure of the tetrameric lac repressor-DNA complex was determined by the group of Mitchell Lewis, University of Pennsylvania, Philadelphia, and the dimeric PurR-DNA complex by the group of Richard Brennan, Oregon Health Sciences University, Portland. 

The polypeptide chain of the lac repressor subunit is arranged in four domains (Figure 8.21) an N-terminal DNA-hinding domain with a helix-turn-helix motif, a hinge helix which binds to the minor groove of DNA, a large core domain which binds the corepressor and has a structure very similar to the periplasmic arablnose-binding protein described in Chapter 4, and finally a C-terminal a helix which is involved in tetramerization. This a helix is absent in the PurR subunit structure otherwise their structures are very similar. 

The tetrameric structure of the lac repressor has a quite unusual V-shape (Figure 8.22). Each arm of the V-shaped molecule is a tight dimer, which is very similar in structure to the PurR dimer and which has the two N-termi-nal DNA binding domains close together at the tip of the arm. The two dimers of the lac repressor are held together at the other end by the four carboxy-terminal a helices, which form a four-helix bundle. 

Figure 9.17 Schematic diagram illustrating the tetrameric stmcture of the pS3 oligomerization domain. The four subunits have different colors. Each subunit has a simple structure comprising a p strand and an a helix joined by a one-residue turn. The tetramer is built up from a pair of dimers (yellow-blue and red-green). Within each dimer the p strands form a two-stranded antiparallel p sheet which provides most of the subunit interactions. The two dimers are held together by interactions between the four a helices, which are packed in a different way from a four-helix bundle. (Adapted from P.D. Jeffrey et al.. Science 267 1498-1502, 1995.)...

Jeffrey, P.D., Gorina, S., Pavletich, N.P. Crystal structure of the tetramerization domain of the p53 tumor suppressor at 1.7 Angstroms. Science 267 1498-1502, 1995. 

All K channels are tetrameric molecules. There are two closely related varieties of subunits for K channels, those containing two membrane-spanning helices and those containing six. However, residues that build up the ion channel. Including the pore helix and the inner helix, show a strong sequence similarity among all K+ channels. Consequently, the structural features and the mechanism for ion selectivity and conductance described for the bacterial K+ channel in all probability also apply for K+ channels in plant and animal cells. 

In the case of phenyllithium, it has been possible to demonstrate by NMR studies that the compound is tetrameric in 1 2 ether-cyclohexane but dimeric in 1 9 TMEDA-cyclohexane. X-ray crystal structure determinations have been done on both dimeric and tetrameric structures. A dimeric structure crystallizes from hexane containing TMEDA. This structure is shown in Fig. 7.1 A. A tetrameric structure incorporating four ether molecules forms from ether-hexane solution. This structure is shown in Fig. 7.IB. There is a good correspondence between the structures that crystallize and those indicated by the NMR studies. 

Tetrameric structures based on distorted cubic structures are also found for (CH3Li)4 and (C2H5Li)4. These tetrameric structures can also be represented as being based on a... 

Fig. 7.1. Crystal structures of phertyllithium (A) dimeric structure incorporating tetra-methylethylenediamine (B) tetrameric structure incorporating dietl l ether., (Reproduced ftom Refs. 28 and 29 with permission of Wiley-VCH and the American Chemical Society.)...

The THF solvate of lithium i-butylacetylide is another example of a tetrameric structure. ... 

Crystal structure determination has also been done with -butyllithium. A 4 1 n-BuLi TMEDA complex is a tetramer accommodating two TMEDA molecules, which, rather than chelating a lithium, link the tetrameric units. The 2 2 -BuLi TMEDA complex has a structure similar to that of [PhLi]2 [TMEDA]2. Both 1 1 -BuLi THF and 1 1 -BuLi DME complexes are tetrameric with ether molecules coordinated at each lithium (Fig. 7.2). These and many other organolithium structures have been compared in a review of this topic. ... 

A more detailed representation of the reaction requires more intimate knowledge of the enolate structure. Studies of ketone enolates in solution indicate that both tetrameric and dimeric clusters can exist Tetrahydrofliran, a solvent in which many synthetic reactions are performed, favors tetrameric structures for the lithium enolate of isobutyr-ophenone, for example. ... 

The structure and bonding in lithium methyl have been particularly fully studied. The crystal structure consists of interconnected tetrameric units (LiMe)4 as shown in Fig. 4.17 the individual Li4C4 clusters consist of a tetrahedron... 

Figure 13.4 (a) ITie cri-bridged polymeric structure of liquid SbFs (schematic) show-ing the three sorts of F alom. (b) Structure of the tetrameric molecular unit in crystalline (SbFs)4 show[Pg.562]

Figure 16.13 Structures of some tetrahalides of Se and Te (a) Sep4 (gas), (b) crystalline Sep4, and schematic representation of the association of the pseudo-tbp molecules (see text), (c) coordination environment of Te in crystalline Tep4 and schematic representation of the polymerized square pyramidal units, (d) the tetrameric unit in crystalline (TeCl4)4, and (e) two representations of the tetrameric molecules in Te4li6 showing the shared edges of the Telg octahedral subunits.

Figure 22.4 Alternative representations of (a) infinite chains of vanadium atoms in VF5, (b) tetrameric structures of NbFs and TaFs, and (c) dimeric structure of MX5 (M = Mb, Ta X = Cl, Br).

The pentafluorides of Rh and Ir may be prepared by the deliberate thermal dissociation of the hexafluorides. They also are highly reactive and are respectively dark-red and yellow solids, with the same tetrameric structure as [Rup5]4 and [Osp5]4 (p. 1083). 

LCo(H20)6] ion, and bidentate /V-donor ligands such as cn, bipy and phen form octahedral cationic complexes [Co(L-L)3] , which are much more stable to oxidation than is the hexaammine [Co(NH3)6l . Acac yields the orange [Co(acac)2(H20)2] which has the tram octahedral structure and can be dehydrated to [Co(acac)2l which attains octahedral coordination by forming the tetrameric species shown in Fig. 26.3. This is comparable with the trimeric [Ni(acac>2]3 (p. 1157), like which it shows evidence of weak ferromagnetic interactions at very low temperatures. fCo(edta)(H20)] is ostensibly analogous to the 7-coordinate Mn and complexes with the same stoichiometry, but in fact the cobalt is only 6-coordinate, 1 of the oxygen atoms of the cdta being too far away from the cobalt (272 compared to 223 pm for the other edta donor atoms) to be considered as coordinated. 

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