Metals in Biochemistry Notes PDF

Amino Acids and Proteins See also separate documents on Canvas Metals in...

Amino Acids and Proteins See also separate documents on Canvas Metals in Amino acids.pdf Biochemistry/Biology Protein Structures.pdf Amino acids Dr Nigel Young Chemistry (School of Natural Sciences) [email protected] The twenty common amino acids Henderson-Hasselbalch equation Alanine (Ala, A, 89, 71) Arginine (Arg, R , 174, 156) Asparagine (Asn, N, 132, 114) Aspartic acid (Asp, D, 133, 115) HA HA HA 𝑝𝐾 = 𝑝𝐻 + log 𝑝𝐻 = 𝑝𝐾 − log log = 𝑝𝐾 − 𝑝𝐻 𝐴 𝐴 𝐴 Cysteine (Cys, C, 121, 103) Glutamatic acid (Glu, E, 147, 129) Glutamine (Gln, Q, 146, 128) Glycine (Gly, G, 75, 57) This tells us that pKa = pH when log[HA]/[A−] = 0, i.e. when [HA] = [A−], or when the concentration of the acid HA is Histidine (His, H, 155, 137) Isoleucine (Ile, I, 131, 113) Leucine (Leu, L, 131, 113) Lysine (Lys, K, 146, 128) equal to the concentration of its conjugate base A−. We need to remember that pKa is a fundamental property of the acid, whereas pH is something we can adjust. Methionine (Met, M, 149, 131) Phenylalanine (Phe, F, 165, 147) Proline (Pro, P, 115, 97) Serine (Ser, S, 105, 87) Using the Henderson-Hasselbalch equation we can see that when pH < pKa, log[HA]/[A−] has to be > 0, so [HA] > [A−], i.e. the Threonine (Thr, T, 119, 101) Tryptophan (Trp, W, 204, 186) Valine (Val, V, 117, 99) protonated form, HA, will be present Tyrosine (Tyr, Y, 181, 163) pH > pKa, log[HA]/[A−] has to be < 0, so [HA] < [A−], i.e. the deprotonated form, A−, will be present  pKa for –COOH is ca. 2.2 and pKa for -NH3+ is ca. 9.5 Therefore at physiological pH (ca. 7) the amino acids are present as zwitterions containing COO− and NH3+ O OH O NH2 Aspart Arginine (Arg, R , 174, 156, pka 12.48) OH Alanine (Ala, A, 89, 71) Asparagine (Asn, N, 132, 114) acid (Asp, D, 133, 115) NH2 O Methionine (Met, M, 149, 131) Proline (Pro, P, 115, 97) Serine (Ser, S, 105, 87) Phenylalanine (Phe, F, 165, 147) OH Glutamatic NH2 Cysteine (Cys, C, 121, 103, pKa 8.35) acid (Glu, E, 147, 129, pKa 4.25) Glutamine (Gln, Q, 146, 128) Glycine (Gly, G, 75, 57) Threonine (Thr, T, 119, 101) Tryptophan (Trp, W, 204, 186) Valine (Val, V, 117, 99) Tyrosine (Tyr, Y, 181, 163, pKa 10.13) Isoleucine (Ile, I, 131, 113) Leucine (Leu, L, 131, 113) Lysine (Lys, K, 146, 128, pKa 10.79 Histidine (His, H, 155, 137, pKa 6.00)  The pKa values of the side chains also allow us to Therefore, a side chain pKa of 3.65 for aspartic acid predict the form of these present at means that the acid side chain group will be physiological/biological pH. deprotonated and it will be present as aspartate From the considerations above a pKa of less than 7 with a COO− group. will result in a deprotonated carboxylic acid, and a The same is true for glutamic acid , and a side chain pKa of greater than 7 will result in a protonated pKa of 4.25 for glutamic acid means it will be group such as amine, hydroxyl, thiol. present at glutamate with a COO− group available for coordination to metals. The pKa of 6.00 for the imidazole NH group Although the pKa values of 8.35 and 10.13 for indicates that this will be present as NH rather than cysteine would indicate that these would be NH2+, but coordination is through the imine N. present as -SH and -OH groups it should be The side chain pKa of 10.79 for lysine means that remembered that coordination of a metal increases the side chain amino group will be present as – the acidity of these groups, so both tyrosine and (CH2)4-NH3+ at physiological pH, and is unlikely to cysteine can act as ligands towards metal ions. act as a ligand for metals. Likewise, with a pKa pf 12.48, the side chain in arginine will be present as –(CH2)-NH-C(=NH)-NH3+.  Some metal-binding groups of importance in biology OH N N N N N O H N H H N Mg H N N N N N Me OH R porphyrin O The amino acids that commonly function as ligands MeO2C O protoporphyrin IX chlorin ring of chlorophylls (iron complex is called haem) are the thiolate of cysteine, the imidazole of O histidine, the carboxylates of glutamic and aspartic HN - O O Mo O O S N N N N acid, and the phenolate of tyrosine. H N S H Ni H HN N N N N O H 2N N N O PO32- Less frequently encountered are the hydroxyl H corrin (e.g. cobalt complex in vitamin B-12) molybdenum cofactor in oxo transfer proteins (probable structure) O groups of serine and threonine, the thioether of nickel(II) hydroporphyrin of Factor F430 (ring substituents omitted for clarity) methionine, the carboxamide groups of glutamine and asparagine, the amino group of lysine and O H H N N HO O OH possibly the guanidine group of arginine. OH O O O O O OH O O NH OH OH enterobactin Proteins Made up of amino acids Metals in How connected to each other Biochemistry/Biology Peptide bonds Proteins Dr Nigel Young Chemistry (School of Natural Sciences) [email protected] Protein structures Primary protein structure primary Amino acids are joined together by peptide bonds secondary Primary structure is order of amino acids in the tertiary polypeptide or protein backbone. quartenary Secondary protein structure This describes the three dimensional orientation of the proteins. Controlled by Hydrogen bonds Between carbonyl oxygen of one amino acid and amino hydrogen of a different amino acid  Two distinct structural types which are represented by coils and arrows. The coils are called α-helices, The arrows are called β-sheets, or β-pleated sheets. α – helix One of the two common motifs in the secondary structure of proteins. Every N-H group in the protein backbone hydrogen bonds to a C=O group also in the backbone, but located four residues earlier in the protein sequence. This forms a right-handed helical structure, where each turn of this helix contains 3.6 amino acids. The R groups of the amino acids which define the primary structure point out from the helix, meaning that they are able to interact with for example metals. β-sheet The β-sheet, or β-pleated sheet is the second The R groups of the amino acid residues protrude important structural motif found in the secondary alternately above and below the plane of the β- structure of proteins. sheet. β-sheets consist of β-strands connected laterally by The β-strand is typically 3 to 10 amino acids long. hydrogen bonds between two (or more) The arrows point from the amino (N-terminus) polypeptide chains. towards the carboxyl (C-terminus) residues. The amide hydrogen of one amino acid is located opposite the carboxy oxygen of another one. This forms a twisted, pleated sheet.  The individual strands may either be parallel, where they point in the same direction (i.e. the N- and C- anti-parallel parallel termini match up) or antiparallel, pointing in opposite directions (i.e. the N-terminus from one strand is located next the C-terminus of the other). The anti-parallel arrangement produces the strongest inter-strand stability because the hydrogen bonds formed are planar Tertiary structure This is the overall structure When protein folding takes place, the hydrophobic Largely determined by interactions R groups from the non-polar amino acids lie within of the R groups of the amino acids. the protein interior resulting in hydrophobic interactions. hydrogen bonding The hydrophilic R groups are on the outside. ionic bonding dipole-dipole interactions London dispersion forces Covalent bonding (disulfide bridges between two cysteines.  Quartenary structures Some proteins, such as hemoglobin, form from several smaller proteins or polypeptides, and it is the interaction of these sub-units that results in the quaternary structure. Myoglobin is just one unit, but hemoglobin has four sub-units https://openstax.org/books/biology-2e/pages/3-4-proteins#fig-ch03_04_09