Small molecules are used as inhibitors of protein action - as drugs. They most often do this by blocking the active site within the protein. Potential drugs can be screened computationally to determine if they are strongly bound to the protein. Figure 1 shows a possible conformation of a candidate drug molecule, 4-bromo-2- carboxymethylamide-pyrrole (abbreviation: BCMAP) at the active site of a protein (abbreviation: PR). Figure 2 shows the full protein structure whilst figure 3 shows a known inhibitor of the protein at the site, overlayed with another calculated conformer of BCMAP. (b) Outline how you would identify likely geometries of BCMAP in the binding site of PR. You need to consider different conformers of BCMAP but only the single active site in PR. Explain how you would rank the more probable geometries for comparison to experimental data on known inhibitors (such as in Figure 3). You should comment on any approximations to the protein structure that may be necessary or reasonable to make. Figure 1. 4-bromo-2-carboxymethylamide-pyrrole (BCMAP) (C, N, O, and Br atoms in yellow, blue, red, and brown, respectively) in the active site of the protein structure.
Small molecules are used as inhibitors of protein action - as drugs. They most often do this by blocking the active site within the protein. Potential drugs can be screened computationally to determine if they are strongly bound to the protein. Figure 1 shows a possible conformation of a candidate drug molecule, 4-bromo-2- carboxymethylamide-pyrrole (abbreviation: BCMAP) at the active site of a protein (abbreviation: PR). Figure 2 shows the full protein structure whilst figure 3 shows a known inhibitor of the protein at the site, overlayed with another calculated conformer of BCMAP. (b) Outline how you would identify likely geometries of BCMAP in the binding site of PR. You need to consider different conformers of BCMAP but only the single active site in PR. Explain how you would rank the more probable geometries for comparison to experimental data on known inhibitors (such as in Figure 3). You should comment on any approximations to the protein structure that may be necessary or reasonable to make. Figure 1. 4-bromo-2-carboxymethylamide-pyrrole (BCMAP) (C, N, O, and Br atoms in yellow, blue, red, and brown, respectively) in the active site of the protein structure.
Human Anatomy & Physiology (11th Edition)
11th Edition
ISBN:9780134580999
Author:Elaine N. Marieb, Katja N. Hoehn
Publisher:Elaine N. Marieb, Katja N. Hoehn
Chapter1: The Human Body: An Orientation
Section: Chapter Questions
Problem 1RQ: The correct sequence of levels forming the structural hierarchy is A. (a) organ, organ system,...
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Enzyme kinetics
In biochemistry, enzymes are proteins that act as biological catalysts. Catalysis is the addition of a catalyst to a chemical reaction to speed up the pace of the reaction. Catalysis can be categorized as either homogeneous or heterogeneous, depending on whether the catalysts are distributed in the same phase as that of the reactants. Enzymes are an essential part of the cell because, without them, many organic processes would slow down and thus will affect the processes that are important for cell survival and sustenance.
Regulation of Enzymes
A substance that acts as a catalyst to regulate the reaction rate in the living organism's metabolic pathways without itself getting altered is an enzyme. Most of the biological reactions and metabolic pathways in the living systems are carried out by enzymes. They are specific for their works and work in particular conditions. It maintains the best possible rate of reaction in the most stable state. The enzymes have distinct properties as they can proceed with the reaction in any direction, their particular binding sites, pH specificity, temperature specificity required in very few amounts.
Question
Transcribed Image Text:Small molecules are used as inhibitors of protein action - as drugs. They most often do this
by blocking the active site within the protein. Potential drugs can be screened
computationally to determine if they are strongly bound to the protein.
Figure 1 shows a possible conformation of a candidate drug molecule, 4-bromo-2-
carboxymethylamide-pyrrole (abbreviation: BCMAP) at the active site of a protein
(abbreviation: PR). Figure 2 shows the full protein structure whilst figure 3 shows a known
inhibitor of the protein at the site, overlayed with another calculated conformer of BCMAP.
(b) Outline how you would identify likely geometries of BCMAP in the binding site of PR.
You need to consider different conformers of BCMAP but only the single active site in
PR. Explain how you would rank the more probable geometries for comparison to
experimental data on known inhibitors (such as in Figure 3). You should comment on
any approximations to the protein structure that may be necessary or reasonable to
make.
Figure 1. 4-bromo-2-carboxymethylamide-pyrrole (BCMAP) (C, N, O, and Br atoms in yellow, blue,
red, and brown, respectively) in the active site of the protein structure.
Transcribed Image Text:Figure 2. Cartoon (ribbon) structure of the entire protein with a known inhibitor in position, as
determined experimentally. Cations and water molecules in the protein structure are omitted for
clarity. The links labelled can be cleaved chemically.
lle1122
Cleavable
Links
Leul120
Tyr1167
Asn1168
Val1174
Prol110
Figure 3. An overlay of a known inhibitor (from Figure 2) and an example conformer of BCMAP. Dashed
lines indicate hydrogens bonds and electrostatic interactions. The isolated cyan atoms are sodium
cations and the isolated red atoms the determined positions of the oxygen in a water molecule.
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