Structure of tryptophan

Figure 5.22 Chemical structures of tryptophan and cysteine as subunits of a protein chain...

Figure 24.19. Structure of Tryptophan Synthetase. The structure of the complex formed by one a subunit and one P lb subunit. PLP is bound to the P subunit.

Figure 4 Chemical structures of tryptophan and of contaminants EBT and PAA associated with EMS.

NAD and NADP can be produced from the ring structure of tryptophan. Therefore, tryptophan spares the dietary requirement for niacin. The higher the dietary levels of tryptophan, the lower the levels of niacin required to prevent symptoms of deficiency. 

The pathway for the synthesis of serotonin from tryptophan is very similar to the pathway for the synthesis of norepinephrine from tyrosine (Fig. 48.7). The first enzyme of the pathway, tryptophan hydroxylase, uses an enzymic mechanism similar to that of tyrosine and phenylalanine hydroxylase and requires BH4 to hydroxylate the ring structure of tryptophan. The second step of the pathway is a decarboxylation reaction... 

Describe the structure of tryptophan synthetase and the role of substrate channeling in its catalytic reaction. 

Fig. 15. Two views of the crystal structure of tryptophan synthase. Side view showing both domains and top view showing the channel [94]...

The crystal structure of tryptophan synthase was retrieved from the Brookhaven Protein data bank see Schneider TR, Gerhardt E, Lee M, Liang P-H, Anderson KS, Schlichting I (1998) Biochem 37 5394... 

The ligand-bound structure of tryptophan 2,3-dioxygenase (PDB 2NW7). 

SCHEME 4 Structures of tryptophan-based surfactants of glycerol ether type. 

The near-UV CD fine structure of tryptophan and seven of its derivatives were examined by employing high-resolution spectra recorded at 77° K 389). The spectra may be grouped into four classes i) Lb bands intense, ii) La bands intense, iii) both La and Lb bands intense, iv) fine structure whose origin was not readily identified. Both the 0-0 and 0- - 850 cm Lb transitions occur together (near 290 and 283 nm, respectively) and have the same CD sign. A number of La transitions were identified, but their relative intensities varied greatly. 

Figure 3.2. Crystal structures of (upper left) Cu(L-tryptophan)(2,2 bipyridine) CIO 4 (upper right) Cu(L-Tryptophan)(1, l()-phenanthroline)ClO4 . 5H2O and (lower) Cu(L-...

Figure 4.7 Two of the enzymatic activities involved in the biosynthesis of tryptophan in E. coli, phosphoribosyl anthranilate (PRA) isomerase and indoleglycerol phosphate (IGP) synthase, are performed by two separate domains in the polypeptide chain of a bifunctional enzyme. Both these domains are a/p-barrel structures, oriented such that their active sites are on opposite sides of the molecule. The two catalytic reactions are therefore independent of each other. The diagram shows the IGP-synthase domain (residues 48-254) with dark colors and the PRA-isomerase domain with light colors. The a helices are sequentially labeled a-h in both barrel domains. Residue 255 (arrow) is the first residue of the second domain. (Adapted from J.P. Priestle et al., Proc.

Hyde, C.C., et al. Three-dimensional structure of the tryptophan synthase az pz multienzyme complex from Salmonella typhimurium. J. Biol. Chem. 263 17857-17871, 1988. 

The elegant genetic studies by the group of Charles Yanofsky at Stanford University, conducted before the crystal structure was known, confirm this mechanism. The side chain of Ala 77, which is in the loop region of the helix-turn-helix motif, faces the cavity where tryptophan binds. When this side chain is replaced by the bulkier side chain of Val, the mutant repressor does not require tryptophan to be able to bind specifically to the operator DNA. The presence of a bulkier valine side chain at position 77 maintains the heads in an active conformation even in the absence of bound tryptophan. The crystal structure of this mutant repressor, in the absence of tryptophan, is basically the same as that of the wild-type repressor with tryptophan. This is an excellent example of how ligand-induced conformational changes can be mimicked by amino acid substitutions in the protein. 

Figure 8.20 Schematic diagrams of docking the trp repressor to DNA in its inactive (a) and active (b) forms. When L-tryptophan, which is a corepressor, hinds to the repressor, the "heads" change their positions relative to the core to produce the active form of the repressor, which hinds to DNA. The structures of DNA and the trp repressor are outlined.

Zhang, R.-G., et al. The crystal structure of trp aporepressor at 1.8 A shows how binding tryptophan enhances DNA affinity. Nature 327 591-S97, 1987. 

Conversely, when A-alkyl tryptophan methyl esters were condensed with aldehydes, the trans diastereomers were observed as the major products." X-ray-crystal structures of 1,2,3-trisubstituted tetrahydro-P-carbolines revealed that the Cl substituent preferentially adopted a pseudo-axial position, forcing the C3 substituent into a pseudo-equatorial orientation to give the kinetically and thermodynamically preferred trans isomer." As the steric size of the Cl and N2 substituents increased, the selectivity for the trans isomer became greater. A-alkyl-L-tryptophan methyl ester 42 was condensed with various aliphatic aldehydes in the presence of trifluoroacetic acid to give predominantly the trans isomers. ... 

The structure of the complex of (S)-tryptophan-derived oxazaborolidine 4 and methacrolein has been investigated in detail by use of H, B and NMR [6b. The proximity of the coordinated aldehyde and indole subunit in the complex is suggested by the appearance of a bright orange color at 210 K, caused by formation of a charge-transfer complex between the 7t-donor indole ring and the acceptor aldehyde. The intermediate is thought to be as shown in Fig. 1.2, in which the s-cis conformer is the reactive one. 

Transition state theory, 46,208 Transmission factor, 42,44-46,45 Triosephosphate isomerase, 210 Trypsin, 170. See also Trypsin enzyme family active site of, 181 activity of, steric effects on, 210 potential surfaces for, 180 Ser 195-His 57 proton transfer in, 146, 147 specificity of, 171 transition state of, 226 Trypsin enzyme family, catalysis of amide hydrolysis, 170-171. See also Chymotrypsin Elastase Thrombin Trypsin Plasmin Tryptophan, structure of, 110... 

Neurotoxins present in sea snake venoms are summarized. All sea snake venoms are extremely toxic, with low LD5Q values. Most sea snake neurotoxins consist of only 60-62 amino acid residues with 4 disulOde bonds, while some consist of 70 amino acids with 5 disulfide bonds. The origin of toxicity is due to the attachment of 2 neurotoxin molecules to 2 a subunits of an acetylcholine receptor that is composed of a2 6 subunits. The complete structure of several of the sea snake neurotoxins have been worked out. Through chemical modification studies the invariant tryptophan and tyrosine residues of post-synaptic neurotoxins were shown to be of a critical nature to the toxicity function of the molecule. Lysine and arginine are also believed to be important. Other marine vertebrate venoms are not well known. 

Figure 13.7 Synthesis and structure of the trace amines phenylethylamine, /)-tyramine and tryptamine. These are all formed by decarboxylation rather than hydroxylation of the precursors of the established monoamine neurotransmitters, dopamine and 5-HT. (1) Decarboxylation by aromatic L-amino acid decarboxylase (2) phenylaline hydroxylase (3) tyrosine hydroxylase (4) tryptophan hydroxylase...

Both enzymes belong to the family of a,p-hydrolases." The active site of MeHNL is located inside the protein and connected to the outside through a small channel, which is covered by the bulky amino acid tryptophane 128." It was possible to obtain the crystal structure of the complex with the natural substrate acetone cyanohydrin with the mutant SerSOAla of MeHNL. This complex allowed the determination of the mode of substrate binding in the active site." A summary of 3D structures of known HNLs was published recently." " ... 

Typically, neurotoxic effects of drugs on monoamine neurons have been assessed from reductions in brain levels of monoamines and their metabolites, decreases in the maximal activity of synthetic enzymes activity, and decreases in the active uptake carrier. In the present study, the traditional markers described above have been used, including the measurement of the content of monoamines and their metabolites in brain at several different timepoints following drug administration. Since reports in the literature have documented that MDMA and MDA can inhibit the activity of tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin synthesis (Stone et al. 1986 Stone et al. 1987). it is unclear whether MDMA-induced reductions in the content of serotonin and its metabolite 5-hydroxyin-doleacetic acid (5-HlAA) may be due to suppressed neurotransmission in otherwise structurally intact serotonin neurons or may represent the eonsequenee of the destruction of serotonin neurons and terminals. 

---