Lipid-binding proteins adipocyte

Evidence has accumulated that the interaction of ALBP and HSL constitutes an additional mechanism whereby the hydrolytic activity of HSL is regulated (Pig. 11.7, step 5). Thus incubation of ALBP with purified recombinant HSL in vitro led to an increase in TAG hydrolysis [286]. This ALBP-induced increase in hydrolytic activity was due to at least two components. First, a small non-specific effect of added ALBP, perhaps altering the surface tension of the TAG substrate and thereby leading to interfacial activation of HSL, and, second, a specific effect. 

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LaLonde, J.M., Levenson, M.A., Roe,J.J., Bemlohr, D.A. and Banaszak, L.J. (1994) Adipocyte lipid-binding protein complexed with arachidonic acid titration calorimetry and X-ray crystallographic studies. Journal of Biological Chemistry 269, 25339-25347. 

Shen, W.-E., Sridhar, K., Bernlohr, D.A. and Kraemer, F.B. (1999) Interaction of rat hormone-sensitive lipase with adipocyte lipid-binding protein. Proceedings of the National Academy of Sciences USA 96, 5528—5532. 

A semi-synthetic metalloenzyme that catalyses the enantioselective hydrolysis of simple amino acid esters has been reported. Iodoacetamido-l,10-phenanthroline (238) was interacted with a cysteine residue in adipocyte lipid binding protein (ALBP) to produce the conjugate ALBP-Phen (239), which was converted into its Cu(II) complex. The ALBP-Phen-Cu(II) was found to catalyse the enantioselective... 

The blue netlike surface in Plate 2 is also a contour map of a three-dimensional function. It represents a surface on which the electron density p(x,y,z) of adipocyte lipid binding protein (ALBP) is constant. Imagine that the net encloses 98% (or some specified value) of the protein s electron density, and so the net is in essence an image of the protein s surface. 

Following is a somewhat idealized description of how map fitting may proceed, illustrated with views from a modern map-fitting program. The maps and models are from the structure determination of adipocyte lipid binding protein (ALBP), which I will discuss further in Chapter 8. 

Z. Xu, D. A. Bemlohr, and L. J. Banaszak, Crystal structure of recombinant murine adipocyte lipid-binding protein, Biochemistry 31,3484-3492, 1992. 

Adipocyte lipid-binding protein (ALBP) is the adipocyte member of an intracellular hydrophobic ligand-binding protein family. ALBP is phosphorylated by the insulin receptor kinase upon insulin stimulation. The crystal structure of recombinant murine ALBP has been determined and refined to 2.5 A. The final R-factorfor the model is 0.18 with good canonical properties. 

Reese-Wagoner, A., et al., Structural properties of the adipocyte lipid binding protein. Biochim Biophys Acta, 1999, 1441, 106-116. 

Figure 6 Introduction of non-native metal cofactors by covalent attachment, (a) Computer model of a phenanthroline complex bound to adipocyte lipid binding protein, (b) Computer model of a dual covalently attached Mn Salen. (Reproduced from Reference 62, p. 11644, copyright 1997 and Reference 63, p. 10812, copyright 2004 with permission from The American Chemical Society.)...

Adipocyte lipid-binding protein ALBP 1.6 Xurtol. (1993)... 

W.-J. Shen, K. Sridhar, D.A. Bernlohr, and F.B. Kraemer, Interaction of rat hormone-sensitive hpase with adipocyte lipid-binding protein, Proc. Natl. Acad. Sci. USA, 1999, 96, 5528-5532. 

N.R. Coe, M.A. Simpson, and D.A. Bernlohr, Targeted disruption of the adipocyte lipid-binding protein (aP2 protein) gene impairs fat cell lipolysis and increases cellular fatty acid levels, J. Lipid Res., 1999, 40, 967-972. 

Figure 5. Three-dimensional and two-dimensional topological representations of flavodoxin (A and B) and adipocyte lipid-binding protein (C and D). In both projections, individual P-strands are numbered in order from the amino- to the carboxyl-terminus.

Figure 22 Introducing nonnative prosthetic group into metalloproteins. (a) by chemical modification of heme propionate. (Reprinted with permission from Ref. 25. 2002 the American Chemical Society) (b) by noncovalent addition strategy. The crystal structure of the Fe (3,3 -Me2-salophen) incorporated into Alal7GlaMb. (Reprinted with permission from Ref. 287. 2004 the American Chemical Society) (c) by a single attachment strategy. The computer model of adipocyte lipid binding protein-phenanthrolme complex. (Reprinted with permission from Ref. 291. 1997 the American Chemical Society) (d) by a dual covalent attachment strategy. The computer model of Mb(L72CA 103C) with a Mn -Salen complex covalently attached at two-points and overlayed with heme. (Reprinted with permission from Ref. 288. 2004 the American Chemical Society)...

Complexes of metal + ligand + protein or DNA can also catalyze the Diels Alder cycloaddition or oxidations with hydrogen peroxide. Copper complexes bound to DNA catalyzed the Diels-Alder cycloaddition with up to 99% ee [15, 16], Cu(phthalocyanine) complexed to serum albumin also catalyzed the enantioselective (98% ee) Diels-Alder reaction, but only with very high catalyst loading (10 mol%) and only with pyridine-bearing dienophiles (presumably to complex the copper) [17]. Achiral Cr(III) complexes or Mn(Schiff-base) complexes inserted into the active site of apomyoglobin variants catalyzed the sulfoxidation of thio-anisole with up to 13 and 51% ee, respectively [18, 19]. A copper phenanthroline complex attached to the adipocyte lipid-binding protein catalyzed the enantioselective hydrolysis of esters and amides [20]. 

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