Question 19.2: Identifying active site side-chain functions Look at the hyd......
Identifying active site side-chain functions
Look at the hydrolysis of a peptide bond by chymotrypsin in Figure 19.4. (a) Which amino acids have side chains that could provide stabilization to the aromatic ring shown in the substrate? (b) What does the serine side chain do in the reaction and why can it do this? (c) What does the histidine side chain do in the reaction and why can it do this?
ANALYSIS Look critically at the diagrams of the reaction in Figure 19.4. Consider each part of the question separately, using the diagrams as an aid. (a) Note that the aromatic ring of phenylalanine fits into a “hydrophobic pocket.” Therefore, the side chains of the amino acids surrounding this pocket in chymotrypsin must be nonpolar.
(b) In the second diagram, note that serine has donated a hydrogen ion to histidine. Remember that acids are proton donors. (c) Also in the second diagram, note that histidine has accepted a proton from serine. Remember that bases are proton acceptors.
(a) Any of the following nonpolar amino acids could be part of the hydrophobic pocket in chymotrypsin: alanine, leucine, isoleucine, methionine, proline, valine, phenylalanine, or tryptophan (see Table 18.3). (b) Serine is a polar amino acid and can donate a proton from the —OH group on the side chain, functioning as an acid. The RO^- remaining can interact with the substrate, initiating cleavage of the substrate. (c) Histidine is a basic amino acid and can accept a proton until needed to complete the cleavage reaction.
In this example, nonpolar amino acids held the substrate in place while amino acids that could act as acids or bases carried out the reaction.
TABLE 18.3 The 20 𝛂-amino acids found in proteins, with their abbreviations and isoelectric points. The structures are written here in their fully ionized forms. These ions and the isoelectric points given in parentheses are explained in Section 18.4.
| Nonpolar , Neutral Side Chains | |
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\begin{matrix} H O\\ H_3\overset{+}{N} — \overset{\mid }{C} — \overset{\mid\mid }{C} — O^-\\ \overset{\mid}{C}H_3\end{matrix} \begin{matrix} H O\\ H_3\overset{+}{N} — \overset{\mid }{C} — \overset{\mid\mid }{C} — O^-\\ \overset{\mid}{H} \end{matrix} \begin{matrix} H O\\ H_3\overset{+}{N} — \overset{\mid }{C} — \overset{\mid\mid }{C} — O^-\\ \overset{\mid}{C}HCH_2 CH_3\\ \overset{\mid}{C}H_3\end{matrix} \begin{matrix} H O\\ H_3\overset{+}{N} — \overset{\mid }{C} — \overset{\mid\mid }{C} — O^-\\ \overset{\mid}{C}H_2CHCH_3\\ \overset{\mid}{C}H_3\end{matrix} Alanine, Ala (6.0) Glycine, Gly (6.0) Isoleucine, Ile (6.0) Leucine, Leu (6.0) \begin{matrix} H O\\ H_3\overset{+}{N} — \overset{\mid }{C} — \overset{\mid\mid }{C} — O^-\\ \overset{\mid}{C}H_2CH_2SCH_3\\ \\ \\ \end{matrix} Methionine, Met (5.7) Phenylalanine, Phe (5.5) Proline, Pro (6.3) Tryptophan, Trp (5.9) Valine, Val (6.0) |
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| Polar , Neutral Side Chains | |
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\begin{matrix} H O\\ H_3\overset{+}{N} — \overset{\mid }{C} — \overset{\mid\mid }{C} — O^-\\ \overset{\mid}{C}H_2C — NH_2\\ \overset{\mid\mid}{O}\end{matrix} \begin{matrix} H O\\ H_3\overset{+}{N} — \overset{\mid }{C} — \overset{\mid\mid }{C} — O^-\\ \overset{\mid}{C}H_2\\ \overset{\mid}{S}H \end{matrix} \begin{matrix} H O\\ H_3\overset{+}{N} —\overset{\mid }{C} — \overset{\mid\mid }{C} — O^-\\ \overset{\mid}{C}H_2CH_2 C — NH_2\\ \overset{\mid\mid}{O}\end{matrix} \begin{matrix} H O\\ H_3\overset{+}{N} — \overset{\mid }{C} — \overset{\mid\mid }{C} — O^-\\ \overset{\mid}{C}H_2\\ \overset{\mid}{O}H\end{matrix} Asparagine, Asn (5.4) Cysteine, Cys (5.0) Glutamine, Gln (5.7) Serine, Ser (5.7) \begin{matrix} H O\\ H_3\overset{+}{N} — \overset{\mid }{C} — \overset{\mid\mid }{C} — O^-\\ \overset{\mid}{C}HCH_3\\ \overset{\mid}{O}H\\ \\ \\ \\ \\ \end{matrix} Threonine, Thr (5.6) Tyrosine, Tyr (5.7) |
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| Acidic Side Chains | Basic Side Chains |
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\begin{matrix} H O\\ H_3\overset{+}{N} — \overset{\mid }{C} — \overset{\mid\mid }{C} — O^-\\ \overset{\mid}{C}H_2C — O^-\\ \overset{\mid\mid}{O}\end{matrix} Aspartic acid, Asp (3.0) (Aspartate) \begin{matrix} H O\\ H_3\overset{+}{N} — \overset{\mid }{C} — \overset{\mid\mid }{C} — O^-\\ \overset{\mid}{C}H_2CH_2C — O^-\\ \overset{\mid\mid}{O}\end{matrix} Glutamic acid, Glu (3.2) |
\begin{matrix}H O \\ H_3\overset{+}{N} — \overset{\mid }{C} — \overset{\mid\mid }{C} — O^- NH_2^+\\ \overset{\mid}{C}H_2CH_2CH_2NH\overset{\mid\mid}{C}NH_2\\ \\ \\ \\ \end{matrix} Arginine, Arg (10.8) Histidine, His (7.6) \begin{matrix} H O\\ H_3\overset{+}{N} — \overset{\mid }{C} — \overset{\mid\mid }{C} — O^-\\ \overset{\mid}{C}H_2CH_2CH_2CH_2\overset{+}{N}H_3\end{matrix}
Lysine, Lys (9.7) |
