Abstract
In protein and RNA macromolecules, only a limited number of different side-chain chemical groups are available to function as catalysts. The myriad of enzyme-catalyzed reactions results from the ability of most of these groups to function either as nucleophilic, electrophilic, or general acid-base catalysts, and the key to their adapted chemical function lies in their states of protonation. Ionization is determined by the intrinsic pKa of the group and the microenvironment created around the group by the protein or RNA structure, which perturbs its intrinsic pKa to its functional or apparent pKa. These pKa shifts result from interactions of the catalytic group with other fully or partially charged groups as well as the polarity or dielectric of the medium that surrounds it. The electrostatic interactions between ionizable groups found on the surface of macromolecules are weak and cause only slight pKa perturbations (<2 units). The sum of many of these weak electrostatic interactions helps contribute to the stability of native or folded macromolecules and their ligand complexes. However, the pKa values of catalytic groups that are found in the active sites of numerous enzymes are significantly more perturbed (>2 units) and are the subject of this review. The magnitudes of these pKa perturbations are analyzed with respect to the structural details of the active-site microenvironment and the energetics of the reactions that they catalyze.
| Original language | English |
|---|---|
| Pages (from-to) | 85-98 |
| Number of pages | 14 |
| Journal | IUBMB Life |
| Volume | 53 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jun 4 2002 |
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Keywords
- Acetoacetate decarboxylase
- Bacteriorhodopsin
- Cysteine protease
- Glycosidase
- Serine protease
- Thioredoxin
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Genetics
- Cell Biology
Cite this
Structural basis of perturbed pKa values of catalytic groups in enzyme active sites. / Harris, Thomas K; Turner, George J.
In: IUBMB Life, Vol. 53, No. 2, 04.06.2002, p. 85-98.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Structural basis of perturbed pKa values of catalytic groups in enzyme active sites
AU - Harris, Thomas K
AU - Turner, George J.
PY - 2002/6/4
Y1 - 2002/6/4
N2 - In protein and RNA macromolecules, only a limited number of different side-chain chemical groups are available to function as catalysts. The myriad of enzyme-catalyzed reactions results from the ability of most of these groups to function either as nucleophilic, electrophilic, or general acid-base catalysts, and the key to their adapted chemical function lies in their states of protonation. Ionization is determined by the intrinsic pKa of the group and the microenvironment created around the group by the protein or RNA structure, which perturbs its intrinsic pKa to its functional or apparent pKa. These pKa shifts result from interactions of the catalytic group with other fully or partially charged groups as well as the polarity or dielectric of the medium that surrounds it. The electrostatic interactions between ionizable groups found on the surface of macromolecules are weak and cause only slight pKa perturbations (<2 units). The sum of many of these weak electrostatic interactions helps contribute to the stability of native or folded macromolecules and their ligand complexes. However, the pKa values of catalytic groups that are found in the active sites of numerous enzymes are significantly more perturbed (>2 units) and are the subject of this review. The magnitudes of these pKa perturbations are analyzed with respect to the structural details of the active-site microenvironment and the energetics of the reactions that they catalyze.
AB - In protein and RNA macromolecules, only a limited number of different side-chain chemical groups are available to function as catalysts. The myriad of enzyme-catalyzed reactions results from the ability of most of these groups to function either as nucleophilic, electrophilic, or general acid-base catalysts, and the key to their adapted chemical function lies in their states of protonation. Ionization is determined by the intrinsic pKa of the group and the microenvironment created around the group by the protein or RNA structure, which perturbs its intrinsic pKa to its functional or apparent pKa. These pKa shifts result from interactions of the catalytic group with other fully or partially charged groups as well as the polarity or dielectric of the medium that surrounds it. The electrostatic interactions between ionizable groups found on the surface of macromolecules are weak and cause only slight pKa perturbations (<2 units). The sum of many of these weak electrostatic interactions helps contribute to the stability of native or folded macromolecules and their ligand complexes. However, the pKa values of catalytic groups that are found in the active sites of numerous enzymes are significantly more perturbed (>2 units) and are the subject of this review. The magnitudes of these pKa perturbations are analyzed with respect to the structural details of the active-site microenvironment and the energetics of the reactions that they catalyze.
KW - Acetoacetate decarboxylase
KW - Bacteriorhodopsin
KW - Cysteine protease
KW - Glycosidase
KW - Serine protease
KW - Thioredoxin
UR - http://www.scopus.com/inward/record.url?scp=0036001159&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036001159&partnerID=8YFLogxK
U2 - 10.1080/15216540211468
DO - 10.1080/15216540211468
M3 - Article
C2 - 12049200
AN - SCOPUS:0036001159
VL - 53
SP - 85
EP - 98
JO - IUBMB Life
JF - IUBMB Life
SN - 1521-6543
IS - 2
ER -