Zinc binding motif

Fig. 3.13. The 3D structure of neprilysin (enkephalinase, EC 3.4.24.11) obtained from ldmt.pdb [79]. This structure was determined for the enkephal-inase-phosphoramidon complex, but the inhibitor has been removed to unmask the catalytic center, a) Structure of the enzyme, with the Glu and the two His residues of the HEXXH zinc-binding motif shown in blue, b) Zoom on the catalytic center, revealing the spatial arrangement of the zinc-binding residues.

Lewis, T.A., Maglathin, R.L. et al. (2008) Human HDAC7 harbors a class Ila histone deacetylase-specific zinc binding motif and cryptic deacetylase activity. 

Hydrogen bond interactions are important for the function of histidine as a zinc ligand. For example, in a survey of zinc-binding motifs, Christianson and Alexander (1989, 1990) reported that head-on and... 

The first zinc binding motif discovered was that of the eucaryotic transcription factor TFIIIA of Xenopus laevis which contains 9 copies of a Cys2His2-Zinc motif The structure of the binding motif is shown in Fig. 1.4. The central zinc ion serves to pack an a-hehx against a P-sheet and thereby position the a-helix. The recognition of the DNA sequence occurs via this a-helix. 

The MMP enzyme family is part of the superfamily of metzincins. The metzincin superfamily is distinguished by a conserved zinc binding motif for the catalytic zinc and a Met-turn region [4]. The MMPs are unique in that they also contain a second structural zinc, however this zinc may be absent in the intact full-length enzyme [5]. The presence of one to four structural calcium ions has been detected in the MMPs that have been characterized to date. The importance of the zinc ions and at least one of the structural calcium ions to enzymatic activity has been proven [6]. 

After translocation into the mitosome, the N-terminal presequences of mitosomal proteins are cleaved off, most likely by a peptidase that is homologous to the mitochondrial processing peptidase (MPP). The MPP is a matrix-localized metallopeptidase with a zinc binding motif His-X-X-Glu-His that is conserved in the putative mitosomal processing peptidase reported in G. intestinalis (Dolezal et al. 2005). 

Melino, S., Rufini, S., Sette, M., Morero, R., Grottesi, A., Paci, M. et al. (1999) Zn2+ ions selectively induce antimicrobial salivary peptide Histatin-5 to fuse negatively charged vesicles. Identification and characterization of a zinc-binding motif present in the functional domain. Biochemistry, 38, 9626-9633. 

Li JY, Jahn R, Dahlstrom A (1994) Synaptotagmin I is present mainly in autonomic and sensory neurons of the rat peripheral nervous system. Neuroscience 63 837-50 Li L, Binz T, Niemann H, Singh BR (2000) Probing the mechanistic role of glutamate residue in the zinc-binding motif of type A botulinum neurotoxin light chain. Biochemistry 39 2399-2405 Ludlow CL, Hallett M, Rhew K, Cole R, Shimizu T et al. (1992) Therapeutic use of type F botulinum toxin. N Engl J Med 326 349-50... 

Deuterolysin from Aspergill us, a Member of Aspzincin Family with a New Zinc-Binding Motif (Hexxh+ D)... 

Very little is known about the structural domains that are responsible for the multiple functions of RNA polymerase. Therefore, comparison of the conserved amino acid sequences of the halobacterial and the eukaryotic enzymes might hint of the possible functional importance of these regions. For instance, the sequence alignment revealed that the zinc-binding motifs suggested for the eukaryotic enzymes are also conserved in the A and B subunits of the H. halobium enzyme, but only the former motif is partially conserved in the P subunit of the E. coli enzyme. Also, the splits of the B and the A subunits of the eukaryotic enzymes into two parts each in the halo-philic enzyme might suggest a division of these subunits into two functional domains. 

FYVE Zinc-binding motif acronym derived from four proteins containing this... 

Fig. 2. Structure and active site of clostridial neurotoxins. The upper panel shows the structure of CNTs, and the segments that show significant homology between the different serotypes are in black (Minton, 1995). The highest homology is shown by a short segment corresponding to the amino acid residues 216-244 in TeTx. This segment contains the zinc-binding motif of metallo-proteinases (zincins) and it is dissimilar to the consensus sequence of the metzincin metallo-proteinase family (Jiang and Bond, 1992)...

The most conserved segment of the L chain of CNTs is a central region that contains a His-Glu-Xaa-Xaa-His zinc-binding motif characteristic of zinc-endopeptidases, thus suggesting that TeTx and the BoNTs may inhibit neuroexocytosis through a zinc-endopeptidase activity. This hypothesis was confirmed with two experimental approaches in Aply-sia neurons. First, the lack of toxicity of the apo-TeTx L chain demonstrated the essential role of the metal atom in toxin activity (Schiavo et ai, 1992 a, b). Second, phosphoramidon, a very specific inhibitor of zinc-endopeptidases, was shown to inhibit TeTx-induced blockade of ACh release (Schiavo ef ai, 1992 b). These results were the first clear evidence that the L chain of TeTx was acting via a metallo-protease activity. 

Fig. 8.1 Classification of metallopeptidases by zinc-binding motifs. The major amino acid motif in zincins has two histidine residues that coordinate with the metal ion and a glutamate residue (E) for catalysis. A third residue that coordinates with the metal may be glutamate, aspartate (D), or histidine. In metzincins, the third coordinating residue is histidine or aspartate (H/D), but the name is taken from the presence of a downstream invariant methionine residue (see Fig. 8.2 and text). The red type indicates enzymes or enzyme subfamilies encoded in the human genome (Slightly modified from Fig. 1A of F.X. Gomis-Ruth, Structural aspects of the metzincin clan of metal-loendopeptidases. Mol. Biotechnol. 24(2) 157-202, 2003)...

Fig.8.3 Architecture of astacins, adamalysin type-2, and matrix metalloproteases. Topology scheme of astacins, adamalysin type-2, and matrix metalloproteinases. The a-helices are shown as rods, 3-sheet strands as arrows, and unstructured regions as thin lines. Key amino acids in the catalytic, zinc-binding motif are shown (white in black ellipse). Distinguishing features of each structure are shown as lighter gray for amino acids (black letter), and as unlabeled, secondary-structure elements. In addition to the catalytic zinc ion in all three structures, the calcium ion in adamalysin type-2, and the two calcium ions and second zinc ion in the matrix metalloproteinases (Abbreviated from Fig. 3 in F.X. Gomis-Ruth, Structural aspects of the metzincin clan of metalloendopepti-dases. Mol. Biotechnol. 24(2) 157-202, 2003)...

Proteins which have the consensus HexxHxxgxxH, where the separation between the first and third (histidine) zinc ligands is nine residues. When the primary sequence in regions other than the zinc binding motif are considered, these proteases to be grouped into four [4, 5,33] classes (Fig. 2). Since most of the zinc proteases are multimodular proteins, with indi-... 

The structures of two Zn-binding motifs are shown in Fig. 1.4. The zinc binding motifs play, above all, a structuring role by ensuring that a recognition helix is correctly oriented and stabilized. The zinc ion does not contact the DNA directly. 

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