Crystal structures lysine

Renatns, M., Engh, R. A., Stubbs, M. T, et al., 1997. Lysine-156 promotes the anomalons proenzyme activity of tPA X-ray crystal structure of singlechain human tPA. EMBO Journal 16 4797-4805. 

Figure 5.9 Models of hexo-kinase in space-filling and wireframe formats, showing the cleft that contains the active site where substrate binding and reaction catalysis occur. At the bottom is an X-ray crystal structure of the enzyme active site, showing the positions of both glucose and ADP as well as a lysine amino acid that acts as a base to deprotonate glucose.

L-piperidine-2-carboxylic acid is a non-proteinogenic amino acid that is a metabolite of lysine. The zinc complexes of DL-piperidine-2-carboxylic acid, DL-piperidine-3-carboxylic acid, and piperidine-4-carboxylic acid have been studied. The X-ray crystal structures have been determined for the latter two. [ZnCl2(DL-piperidine 3-carboxylate)2] (42) is monomeric with a tetrahedral metal center and monodentate carboxylates. [Zn2Cl4(piperidine-4-carboxylate)2] (43) contains two bridging carboxylates in a dimeric structure. IR studies suggest that the DL-piperidine-2-carboxy-lato zinc has monodentate carboxylate ligands coordinating.392... 

Protein biotinylation is catalyzed by biotin protein ligase (BPL). In the active site of the enzyme, biotin is activated at the expense of ATP to form AMP-biotin the activated biotin can then react with a nucleophile on the targeted protein. BPL transfers the biotin to a special lysine on biotin carboxyl carrier protein (BCCP), a subunit of AcCoA carboxylase (Scheme 21). Biotinylation of BCCP is very important in fatty acid biosynthesis, starting the growth of the fatty acid with AcCoA carboxylase to generate malonyl-CoA. Recently the crystal structures of mutated BPL and BCCP have been solved together with biotin and ATP to get a better idea of how the transfer fiinctions. ... 

In mammals a single PPTase is used for the posttranslational modification of three different apo-proteins the carrier proteins of mitochondrial and cytosolic FASs and the aminoadipate semialdehyde reductase implicated in lysine degradation. The crystal structure of human PPT ase has been determined and found to be most closely related to the class II Sfp-like enzymes. Architectural and mechanistic differences between the type II human PPTase and the type I bacterial PPTases include a divalent cation coordinated by the a-phosphate of CoA, a Glu and an Asp residue, and three water ligands in type I PPTases versus a divalent cation coordinated by a- and /3-phosphates of CoA, two to three protein side chains, and a water molecule in the human PPT ase. 

It has been shown that JHDMIA demethylates only mono- and dimethyl lysine of histone H3 (H3K36). This was rather unexpected given that the catalytic mechanism of a Jmj C domain does not require a protonated nitrogen, unlike LS D1, and therefore could also have the ability to remove the methyl in all three states. So far, two crystal structures have been deposited in the protein database but without any publication underlining the work. The crystal structures describe two forms of the human JHDMIA lysine demethylase, apo and in a complex with a-ketoglutarate (PDB codes 2yul and 2yu2). 

Chen, Y, Yang, Y, Wang, F., Wan, K., Yamane, K., Zhang, Y. and Lei, M. (2006) Crystal structure ofhuman histone lysine-specific demethylase 1 (LSDl). Proceedings of the National Academy of Sciences of the United States of America, 103 (38), 13956-13961. 

Stavropoulos, P., Blobel, C. and Hoelz, A. (2006) Crystal structure and mechanism ofhuman lysine-spedfic demethylase-1. Nature Structural ej Molecular Biolr, ... 

During the past several years, a variety of crystal structures of histone lysine and arginine methyltransferase in complex with the cofactor analog SAH and/or in complex with peptide substrates have been reported [92]. However, no 3D structure of a complex between a histone methyltransferase (HMT) and an inhibitor has been reported so far. Due to the lack of experimental structures, a variety of molecular modeling and docking studies has been carried out for H MTs in order to understand the structural requirements for inhibitor binding. 

The disclosure of the HDLP crystal structure in 1999 provided a clear framework and starting point for medicinal chemists for the further development of HDAC inhibitors as antitumor agents. It confirmed the suggested general structural requirements of such inhibitors. These proposed requirements and the resemblance of the inhibitors to the acetylated e-amino groups of lysine residues are shown in Fig. 5. 

View of a modified bovine fibrinogen molecule. The 45-nm-long disulfide-linked dimer is composed of three nonidentical polypeptide chains. The N termini of the six chains from the two halves come together in the center in a small globular "disulfide knot." The C termini form globular domains at the ends. The 340-kDa molecule has been treated with a lysine-specific protease which has removed portions of two chains to give the 285-kDa molecule whose crystal structure is shown. Arrows point to attached oligosaccharides. From Brown et at. (2000) Proc. Natl. Acad. Sci. U. S. A. 97, 85-90. Courtesy of Carolyn Cohen. 

---