Tyrosine, structure


Above a pH of about 10 the major species present in a solution ] of tyrosine has a net charge of -2 Suggest a reasonable structure for this species J  [c.1119]

The chemistry of the brain and central nervous system is affected by a group of substances called neurotransmitters, substances that carry messages across a synapse from one neuron to another Several of these neurotransmitters arise from l tyrosine by structural modification and decarboxylation as outlined m Figure 27 5  [c.1126]

Structure of Wool Proteins. The stmcture of wool proteins has been the subject of much research. Methods to solubilize, separate, and determine the amino acid sequence of these proteins have been reviewed (38—40). The proteins of wool basically belong to three groups low sulfur proteins, rich in amino acids that contribute to a-helix formation (glutamic acid, aspartic acid, leucine, lysine, arginine) high sulfur proteins rich in cystine, proline, serine, and threonine and high glycine—tyrosine proteins which are also rich in serine. The groups of proteins that constitute wool are not uniformly distributed throughout the fiber, but are aggregated within the various morphological regions.  [c.343]

Let us now apply the rules for predicting active sites of a/p structures to the topological diagram shown in Figure 4.15. The p sheet has six strands, one of which, number 1, is antiparallel to the others. The remaining five parallel p strands are arranged in a way rather similar to the nucleotide-binding fold (see Figure 4.1b), but here the strand order is 6 5 2 3 4. Alpha helix 2,3 (which connects P strands 2 and 3) and a helix 3,4 are on one side of the P sheet (red helices in Figure 4.15), whereas a helices 4,5 and 5,6 are on the other side (green helices). The switch point is thus between P strands 2 and 5. We would predict that the active site is outside the carboxy end of P strands 2 and 5 and that the loop regions that connect these strands with their respective a helices participate in binding the substrates. These loop regions comprise residues 38-47 and 190-193, respectively. The active site has been identified in the crystal structure by diffusing tyrosine and ATP into the crystals. The enzyme molecules in the crystals are active, so tyrosyl adenylate is formed, but because no tRNA is present, it stays bound to the enzyme.  [c.60]

Figure 4.17 Schematic diagram of bound tyrosine to tyrosyl-tRNA synthetase. Colored regions correspond to van der Waals radii of atoms within a layer of the structure through the tyrosine ring. Red is bound tyrosine green is the end of P strand 2 and the beginning of the following loop region yellow is the loop region 189-192 and brown is part of the a helix in loop region 173-177. Figure 4.17 Schematic diagram of bound tyrosine to tyrosyl-tRNA synthetase. Colored regions correspond to van der Waals radii of atoms within a layer of the structure through the tyrosine ring. Red is bound tyrosine green is the end of P strand 2 and the beginning of the following loop region yellow is the loop region 189-192 and brown is part of the a helix in loop region 173-177.
No three-dimensional structure is yet available for any complete receptor because they are large and membrane bound, and hence difficult to crystallize, and are too large to study by NMR. However, by recombinant DNA techniques it has been possible to crystallize isolated extracellular and intracellular domains of receptor molecules. In this chapter we will give examples of signal recognition by the binding of growth hormone to the extracellular domain of its receptor, and of the intracellular signal response and amplification by G protein and protein tyrosine kinase-linked receptors. We have no detailed stmctural knowledge on how signals are transmitted through the membrane, nor on how receptors are linked to ion channel signaling.  [c.252]

Peptide hormone receptors are sensory machines that direct cells to proliferate, differentiate, or even die. The growth hormone receptor belongs to one class of the cytokine or hematopoietic superfamily of hormone receptors that mediate signals from more than 20 known cytokines such as interleukin, erythropoietin and prolactin, as well as growth factors. Members of this receptor superfamily have a three-domain organization comprising an extracellular ligand-binding domain, a single transmembrane segment, and an intracellular domain that is quite diverse in sequence among the family members. The intracellular domain is structurally not well characterized, but it is known to associate reversibly with different cytoplasmic tyrosine kinases, which transmit the hormone-induced signal to activate a specific family of transcription factors. We shall describe here the crystal structure of the complex between the human growth hormone, GH, and the extracellular domain of its specific receptor, GHR, and compare this structure with that of growth hormone complexed with the prolactin receptor, PLR. These structures were determined by the group of Anthony Kossiakoff, Genentech, San Francisco.  [c.267]

The second group, the tyrosine kinase associated receptors, have cytosolic domains that lack a defined catalytic function. This large and heterogeneous group includes receptors for cytokines as well as for some hormones including growth hormone and prolactin, discussed earlier. These receptors work through associated cytosolic tyrosine kinases, which phosphorylate various target proteins when the receptor binds its ligand. The best characterized of these associated tyrosine kinases are members of the Src family, so called because the first identified member of this family, the transforming agent of Rous sarcoma virus, induces sarcoma tumors of connective tissues. The structure and regulation of Src will be described later in this chapter.  [c.271]

The structures of many SH3 domains have also been determined as an example, Figure 13.28a shows the SH3 domain from the tyrosine kinase Fyn, a member of the Src family, as determined by the group of Ian Campbell, Oxford University, using NMR methods. The SH3 domain consists of a five-stranded up-and-down antiparallel (3 structure, twisted into a barrel comprising two antiparallel p sheets that pack against each other so that their strands are nearly orthogonal. Strand p2 takes part in both sheets. This fold is common to all SH3 modules. The loop regions differ, however, and in some SH3 domains they contain small regions of secondary structure.  [c.274]

C-terminal tail (Tyr 527 in c-Src). Phosphorylation of Tyr 419 activates the kinase phosphorylation of Tyr 527 inhibits it. Crystal structures of a fragment containing the last four domains of two members of this family were reported simultaneously in 1997—cellular Src by the group of Stephen Harrison and Hck by the group of John Kuriyan. The two structures are very similar, as expected since the 440 residue polypeptide chains have 60% sequence identity. The crucial C-proximal tyrosine that inhibits the activity of the kinases was phosphorylated in both cases the activation loop was not.  [c.276]

Figure 13.30 Ribbon diagram of the structure of Src tyrosine kinase. The structure is divided in three units starting from the N-terminus an SH3 domain (green), an SH2 domain (blue), and a tyrosine kinase (orange) that is divided into two domains and has the same fold as the cyclin dependent kinase described in Chapter 6 (see Figure 6.16a). The linker region (red) between SH2 and the kinase is bound to SH3 in a polyproline helical conformation. A tyrosine residue in the carboxy tail of the kinase is phosphorylated and bound to SH2 in its phosphotyrosine-binding site. A disordered part of the activation segment in the kinase is dashed. (Adapted from W. Xu et al.. Nature 385 595-602, 1997.) Figure 13.30 Ribbon diagram of the structure of Src tyrosine kinase. The structure is divided in three units starting from the N-terminus an SH3 domain (green), an SH2 domain (blue), and a tyrosine kinase (orange) that is divided into two domains and has the same fold as the cyclin dependent kinase described in Chapter 6 (see Figure 6.16a). The linker region (red) between SH2 and the kinase is bound to SH3 in a polyproline helical conformation. A tyrosine residue in the carboxy tail of the kinase is phosphorylated and bound to SH2 in its phosphotyrosine-binding site. A disordered part of the activation segment in the kinase is dashed. (Adapted from W. Xu et al.. Nature 385 595-602, 1997.)
C-terminal lobes of the tyrosine kinase are similar to those of cyclin-depen-dent kinase described in Chapter 6 (see Figure 6.16a), while the SH2 and SH3 domains of Src and Hck have structures very similar to those of the isolated domains (see Figures 13.26 and 13.28a).  [c.277]

Figure 13.32 Regulation of the catalytic activity of members of the Src family of tyrosine kinases, (a) The inactive form based on structure determinations. Helix aC is in a position and orientation where the catalytically important Glu residue is facing away from the active site. The activation segment has a conformation that through steric contacts blocks the catalytically competent positioning of helix aC. (b) A hypothetical active conformation based on comparisons with the active forms of other similar protein kinases. The linker region is released from SH3, and the activation segment changes its structure to allow helix aC to move and bring the Glu residue into the active site in contact with an important Lys residue. Figure 13.32 Regulation of the catalytic activity of members of the Src family of tyrosine kinases, (a) The inactive form based on structure determinations. Helix aC is in a position and orientation where the catalytically important Glu residue is facing away from the active site. The activation segment has a conformation that through steric contacts blocks the catalytically competent positioning of helix aC. (b) A hypothetical active conformation based on comparisons with the active forms of other similar protein kinases. The linker region is released from SH3, and the activation segment changes its structure to allow helix aC to move and bring the Glu residue into the active site in contact with an important Lys residue.
Signaling through tyrosine kinase domains is involved in such diverse biological activities as cell growth, cell shape, cell cycle control, transcription and apoptosis. Receptor-associated cytosolic tyrosine kinases contain a set of protein modules such as SH2, SH3, and PH domains that function as adaptors to bring together a kinase domain and its appropriate target. SH2 and SH3 domains recognize short peptide sequences containing phosphotyrosine and proline-rich regions, respectively some PH domains recognize lipid head groups. SH2 domains fold into a central p sheet surrounded by two helices and have a specific phosphotyrosine-binding pocket. SH3 domains fold into a p barrel structure with the peptide-binding site at one end of the barrel, wedged between two loop regions. The peptide region binds in a polyproline type II helix conformation with three residues per turn. Proline-rich sequences favor such a conformation. Additional specificity for target proteins can be provided by interactions between the loop regions and residues of the target protein outside the proline-rich sequence.  [c.279]

Xu, W., Harrison, S.C., Eck, M.J. Three-dimensional structure of the tyrosine kinase c-Src. Nature 385 595-602, 1997.  [c.281]

Yamaguchi, H., Hendrickson, W. Structural basis for activation of human kinase Lck upon tyrosine phosphorylation. Nature 384 484-489, 1996.  [c.281]

Above a pH of about 10, the major species present in a solution of tyrosine has a net charge of -2. Suggest a reasonable structure for this species. J  [c.1119]

The chemistry of the brain and central nervous system is affected by a group of substances called neurotransmitters, substances that cany messages across a synapse from one neuron to another. Several of these neurotransmitters arise from L-tyrosine by structural modification and decarboxylation, as outlined in Figure 27.5.  [c.1126]

Many details of the structure and chemistry of the amino acids have been elucidated or at least confirmed by spectroscopic measurements. None of the amino acids absorbs light in the visible region of the electromagnetic spectrum. Several of the amino acids, however, do absorb ultraviolet radiation, and all absorb in the Infrared region. The absorption of energy by electrons as they rise to higher energy states occurs in the ultraviolet/visible region of the energy spectrum. Only the aromatic amino acids phenylalanine, tyrosine, and tryptophan exhibit significant ultraviolet absorption above 250 nm, as shown in Figure 4.15. These strong absorptions can be used for spectroscopic determinations of protein concentration. The aromatic amino acids also exhibit relatively weak fluorescence, and it has recently been shown that tryptophan can exhibit phos-  [c.99]

A class of slower motions, which may extend over larger distances, is collective motions. These are movements of groups of atoms covalently linked in such a way that the group moves as a unit. Such groups range in size from a few atoms to hundreds of atoms. Whole structural domains within a protein may be involved, as in the case of the flexible antigen-binding domains of immunoglobulins, which move as relatively rigid units to selectively bind separate antigen molecules. Such motions are of two types—(1) those that occur quickly but infrequently, such as tyrosine ring flips, and (2) those that occur slowly, such as cis-trans isomerizations of prolines. These collective motions also arise from thermal energies in the protein and operate on a time scale of 10 to 10 sec. These motions can be studied by nuclear magnetic resonance (NMR) and fluorescence spectroscopy.  [c.182]

Zhang and co-workers worked on the structure-based, computer-assisted search for low molecular weight, non-peptidic protein tyrosine phosphate IB (PTPIB) inhibitors, also using the DOCK methodology [89], They identified several potent and selective PTPIB inhibitors by saeening the ACD.  [c.616]

Signaling through tyrosine kinase domains is involved in a variety of diverse biological processes including cell growth, cell shape, cell cycle control, transcription, and apoptosis (programmed cell death). Receptors regulating cell growth and differentiation were among the first to be studied, and they show a similar overall structural organization (Figure 13.24). The cytosolic region has a tyrosine kinase domain of 250-300 amino acid residues and, in addition, regions that contain tyrosine residues, in different sequence environments, which bind to different adaptor proteins when phosphorylat-ed. The extracellular domains are different for different subclasses of these receptors, but are in many cases built up from immunoglobulin or fibronectin domains. A single transmembrane a helix links the two domains.  [c.271]

Src tyrosine kinase contains both an SH2 and an SH3 domain linked to a tyrosine kinase unit with a structure similar to other protein kinases. The phosphorylated form of the kinase is inactivated by binding of a phosphoty-rosine in the C-terminal tail to its own SH2 domain. In addition the linker region between the SH2 domain and the kinase is bound in a polyproline II conformation to the SH3 domain. These interactions lock regions of the active site into a nonproductive conformation. Dephosphorylation or mutation of the C-terminal tyrosine abolishes this autoinactivation.  [c.280]

The biogenesis of woquinoline alkaloids was also discussed by the late Prof. Barger, who regarded as generally accepted the view that in the heterocychc ring of these bases the nitrogen atom and four atoms of carbon come from an amino-acid and the fifth carbon from an aldehyde as illustrated in the second stage of the norlaudanosine synthesis already referred to. Barger was of opinion that the known structure of many isoquinoline alkaloids and the biological evidence available implies that tyrosine ( -p-hydroxyphenyl-a-aminopropionic acid,  [c.818]

Some proteins play a recently discovered role in the complex pathways of cellular response to hormones and growth factors. These proteins, the scaffold or adapter proteins, have a modular organization in which specific parts (modules) of the protein s structure recognize and bind certain structural elements in other proteins through protein-protein interactions. For example,. S //2 modules bind to proteins in which a tyrosine residue has become phosphorylated on its phenolic —OH, and SH3 modules bind to proteins having a characteristic grouping of proline residues. Others include PH modules, which bind to membranes, and PDZ-containing proteins, which bind specifically to the C-ter-minal amino acid of certain proteins. Because scaffold proteins typically possess several of these different kinds of modules, they can act as a scaffold onto which a set of different proteins is assembled into a multiprotein complex. Such assemblages are typically involved in coordinating and communicating the many intracellular responses to hormones or other signalling molecules (Figure 5.14). Anchoring (or targeting) proteins are proteins that bind other proteins, causing them to associate with other structures in the cell. A family of anchoring proteins, known as AKAP or A kinase anchoring proteins, exists in  [c.124]

Protein kinases are converter enzymes that catalyze the ATP-dependent phosphorylation of serine, threonine, and/or tyrosine hydroxyl groups in target proteins (table). Phosphorylation introduces a bulky group bearing two negative charges, causing conformational changes that alter the target protein s function. (Unlike a phosphoryl group, no amino acid side chain can provide two negative charges.) Protein kinases represent a protein snperfamily whose members are widely diverse in terms of size, subunit structure, and snbcellnlar localization. Nevertheless, all share a common catalytic mechanism based on a conserved catalytic core/kinase domain of approximately 260 amino acid residues (see figure). Protein kinases are classified as Ser/Thr-and/or Tyr-specific and are snbclassified in terms of the allosteric activators they require and the consensus amino acid sequence within the target protein that is recognized by the kinase. For example, cAMP-dependent protein kinase (PKA) phosphorylates proteins having Ser or Thr residues within an R(R/K)X(S /T ) target consensus sequence ( denotes the residue that becomes phosphorylated). That is, PKA phosphorylates Ser or Thr residues that occur in an Arg-(Arg or Lys)-(any amino acid)-(Ser or Thr) sequence segment (table).  [c.466]

Therapeutic Function Antihypertensive Chemical Name 3 hydroxy-a-methyl-L-tyrosine Common Name L-0 -methyl-3,4-dihvdroxyphenvlalanine Structural Formula oh  [c.992]

Therapeutic Function Tyrosine hydroxylase Inhibitor Chetnicel Name tt-Methyl-L-tyrosine Common Name Metirosine Structural Formula  [c.1014]


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Introduction to protein structure (1999) -- [ c.6 , c.59 ]