Citrulline structure

FIGURE 3-8 Uncommon amino acids, (a) Some uncommon amino acids found in proteins. All are derived from common amino acids. Extra functional groups added by modification reactions are shown in red. Desmosine is formed from four Lys residues (the four carbon backbones are shaded in yellow). Note the use of either numbers or Creek letters to identify the carbon atoms in these structures, (b) Ornithine and citrulline, which are not found in proteins, are intermediates in the biosynthesis of arginine and in the urea cycle. 

Absolute Configuration of Citrulline The citrulline isolated from watermelons has the structure shown below. Is it a d- or L-amino acid Explain. 

Figure 19-17 Aptamer that specifically binds citrulline within a pocket in a short stretch of RNA. Long straight lines represent hydrogen-bonded nucleotide bases. The three-dimensional structure was deduced from nuclear magnetic resonance. 

Breakup as indicated by the arrows on this structure would give Fe(III)-OH, citrulline, and 0=N-H, nitroxyl. This is one electron (e + H+) more reduced than NO. Perhaps the adduct forms from Fe(ffl)-0-0. On the other hand, there is evidence that NO synthases may produce nitroxyl or nitroxyl ion NO- as the initial product.537-538 NO and other products such as NzO and N02 may arise rapidly in subsequent reactions. Nitrite is a major oxidation product of NO in tissues.5383 The chemistry of NO in biological systems is complex and not yet fully understood. See also pp. 1754,1755. 

Amino acids are normally known by their trivial names (Table 1.1). In peptide and protein structures their structures are indicated by either three letter groups or single letters (Table 1.1, and Figure 1.7). Amino acids such as ornithine and citrulline, which are not found in naturally occuring peptides and proteins, do not have an allocated three or single letter code (Figure 1.3). 

Figure 2 Stoichiometry of the enzymatic mechanism of formation of NO, and the structure of a competitive inhibitor, N -monomethyl-L-arginine (NMMA). NO is synthesized by all NOS s by a similar mechanism, involving the NADPH-dependent mixed-function oxidation of a guanidino nitrogen of the amino acid L-arginine (L-arg) to produce L-citrulline (L-cit) and -NO. The nonintegral stoichiometries are explained in the text. NMMA inhibits NOS as a competitive inhibitor...

What about the other enzymes in the urea cycle Ornithine transcarbamoylase is homologous to aspartate transcarbamoylase and the structures of their catalytic subunits are quite similar (Figure 23.18). Thus, two consecutive steps in the pyrimidine biosynthetic pathway were adapted for urea synthesis. The next step in the urea cycle is the addition of aspartate to citrulline to form argininosuccinate, and the subsequent step is the removal of fumarate. These two steps together accomplish the net addition of an amino group to citrulline to form arginine. Remarkably, these steps are analogous to two consecutive steps in the purine biosynthetic pathway (Section 25.2 3). 

Figure 9.2. (A) Secondary structure proposed previously for the citrulline- and arginine-specific aptamers, based on co-variations of selected sequences, on the chemical footprinting pattern obtained in the presence of the cognate amino acid, as well as in damage selection experiments. The bases which were conserved among different isolates arc shown in upper case variant bases are in lower case. The three nucleotides critical for arginine specificity (13,29 and 31) arc indicated by circles (for citrulline) and boxes (for arginine). (B) Tertiary structure of the L-arginine aptamer complex resolved by NMR spectroscopy. Yellow L-arginine red the three mutations. (Illustration adapted from [9].)...

Figure 16 Overiay of human DDAH-1 structures bound to the product L-citrulline (tan) and A/ -(2-methoxyethyl)-L-arginine (22) (biue). Protein residues are shown as stick models and ligands as ball-and-stick models. Rearrangements of active-site Leu, His, and Arg residues accommodate the inhibitor, and hold the guanidinium in a nonproductive orientation. The figure was constructed using coordinates from PDB accession codes 2JAJ and 2JAI, respectively.

The structural basis for recognition of protein substrates is not yet clear. However, structures of PAD4 in complex with A -benzoyl-L-arginine amide and peptides from histones H3 and H4 that are known to he citrullinated have provided clues as to how PAD4 hinds and recognizes small molecule substrates. As with ADI and DDAH, the arginine residue of the substrate binds at the center of the propeller of the catalytic domain, and the conserved core residues interact with the guanidine side chain. ... 

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