1cer: Difference between revisions

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DETERMINANTS OF ENZYME THERMOSTABILITY OBSERVED IN THE MOLECULAR STRUCTURE OF THERMUS AQUATICUS D-GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE AT 2.5 ANGSTROMS RESOLUTION

OverviewOverview

The crystal structure of holo D-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from the extreme thermophile Thermus aquaticus has been solved at 2.5 Angstroms resolution. To study the determinants of thermostability, we compare our structure to four other GAPDHs. Salt links, hydrogen bonds, buried surface area, packing density, surface to volume ratio, and stabilization of alpha-helices and beta-turns are analyzed. We find a strong correlation between thermostability and the number of hydrogen bonds between charged side chains and neutral partners. These charged-neutral hydrogen bonds provide electrostatic stabilization without the heavy desolvation penalty of salt links. The stability of thermophilic GAPDHs is also correlated with the number of intrasubunit salt links and total hydrogen bonds. Charged residues, therefore, play a dual role in stabilization by participating not only in salt links but also in hydrogen bonds with a neutral partner. Hydrophobic effects allow for discrimination between thermophiles and psychrophiles, but not within the GAPDH thermophiles. There is, however, an association between thermostability and decreasing enzyme surface to volume ratio. Finally, we describe several interactions present in both our GAPDH and a hyperthermophilic GAPDH that are absent in the less thermostable GAPDHs. These include a four-residue salt link network, a hydrogen bond near the active site, an intersubunit salt link, and several buried Ile residues.

About this StructureAbout this Structure

1CER is a Single protein structure of sequence from Thermus aquaticus with as ligand. Active as Glyceraldehyde-3-phosphate dehydrogenase (phosphorylating), with EC number 1.2.1.12 Full crystallographic information is available from OCA.

ReferenceReference

Determinants of enzyme thermostability observed in the molecular structure of Thermus aquaticus D-glyceraldehyde-3-phosphate dehydrogenase at 25 Angstroms Resolution., Tanner JJ, Hecht RM, Krause KL, Biochemistry. 1996 Feb 27;35(8):2597-609. PMID:8611563

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-[[Image:1cer.gif|left|200px]]<br /><applet load="1cer" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1cer.gif|left|200px]]<br /><applet load="1cer" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1cer, resolution 2.5&Aring;" />
 '''DETERMINANTS OF ENZYME THERMOSTABILITY OBSERVED IN THE MOLECULAR STRUCTURE OF THERMUS AQUATICUS D-GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE AT 2.5 ANGSTROMS RESOLUTION'''<br />
 ==Overview==
-The crystal structure of holo D-glyceraldehyde-3-phosphate dehydrogenase, (GAPDH) from the extreme thermophile Thermus aquaticus has been solved at, 2.5 Angstroms resolution. To study the determinants of thermostability, we, compare our structure to four other GAPDHs. Salt links, hydrogen bonds, buried surface area, packing density, surface to volume ratio, and, stabilization of alpha-helices and beta-turns are analyzed. We find a, strong correlation between thermostability and the number of hydrogen, bonds between charged side chains and neutral partners. These, charged-neutral hydrogen bonds provide electrostatic stabilization without, the heavy desolvation penalty of salt links. The stability of thermophilic, GAPDHs is also correlated with the number of intrasubunit salt links and, total hydrogen bonds. Charged residues, therefore, play a dual role in, stabilization by participating not only in salt links but also in hydrogen, bonds with a neutral partner. Hydrophobic effects allow for discrimination, between thermophiles and psychrophiles, but not within the GAPDH, thermophiles. There is, however, an association between thermostability, and decreasing enzyme surface to volume ratio. Finally, we describe, several interactions present in both our GAPDH and a hyperthermophilic, GAPDH that are absent in the less thermostable GAPDHs. These include a, four-residue salt link network, a hydrogen bond near the active site, an, intersubunit salt link, and several buried Ile residues.
+The crystal structure of holo D-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from the extreme thermophile Thermus aquaticus has been solved at 2.5 Angstroms resolution. To study the determinants of thermostability, we compare our structure to four other GAPDHs. Salt links, hydrogen bonds, buried surface area, packing density, surface to volume ratio, and stabilization of alpha-helices and beta-turns are analyzed. We find a strong correlation between thermostability and the number of hydrogen bonds between charged side chains and neutral partners. These charged-neutral hydrogen bonds provide electrostatic stabilization without the heavy desolvation penalty of salt links. The stability of thermophilic GAPDHs is also correlated with the number of intrasubunit salt links and total hydrogen bonds. Charged residues, therefore, play a dual role in stabilization by participating not only in salt links but also in hydrogen bonds with a neutral partner. Hydrophobic effects allow for discrimination between thermophiles and psychrophiles, but not within the GAPDH thermophiles. There is, however, an association between thermostability and decreasing enzyme surface to volume ratio. Finally, we describe several interactions present in both our GAPDH and a hyperthermophilic GAPDH that are absent in the less thermostable GAPDHs. These include a four-residue salt link network, a hydrogen bond near the active site, an intersubunit salt link, and several buried Ile residues.
 ==About this Structure==
-CER is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermus_aquaticus Thermus aquaticus] with NAD as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Glyceraldehyde-3-phosphate_dehydrogenase_(phosphorylating) Glyceraldehyde-3-phosphate dehydrogenase (phosphorylating)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.1.12 1.2.1.12] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1CER OCA].
+CER is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Thermus_aquaticus Thermus aquaticus] with <scene name='pdbligand=NAD:'>NAD</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Glyceraldehyde-3-phosphate_dehydrogenase_(phosphorylating) Glyceraldehyde-3-phosphate dehydrogenase (phosphorylating)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.1.12 1.2.1.12] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CER OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Single protein]]
 [[Category: Thermus aquaticus]]
-[[Category: Hecht, R.M.]]
+[[Category: Hecht, R M.]]
-[[Category: Krause, K.L.]]
+[[Category: Krause, K L.]]
-[[Category: Tanner, J.J.]]
+[[Category: Tanner, J J.]]
 [[Category: NAD]]
 [[Category: glycolysis]]
@@ Line 22: / Line 22: @@
 [[Category: oxidoreductase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 12:23:51 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:05:22 2008''