Sandbox Reserved 914: Difference between revisions

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The secondary structure of PPT1 contains several α-helices and few β-sheets (Figure 1). PPT1 includes residues 28-306, after the 27-residue signal peptide has been removed <ref name="RSCB">Bellizzi III, John. RCSB Protein Data Bank. PNAS, 18 Apr. 2000.</ref>. An insertion is found between β6 and β7, residues 140-223, and that forms a <scene name='57/573128/9/1'>second domain</scene>, shown in blue, that is compromised almost entirely of the fatty acid binding site. This second domain region contains six helices, α2-α7<ref name="RSCB"/>.

The α/β ~~Hydrolase Fold~~ is common to many other hydrolases. The α/β hydrolase fold has a central 6 stranded parallel β-sheet consisting of <scene name='57/573128/4/1'>β3-β8</scene> and α-helices <scene name='57/573128/5/1'>αA, αB, αC, and αF</scene><ref name="RSCB"/>. ~~It also consists of a~~ catalytic triad and an oxyanion hole~~. The pKa of the nucleophile in the catalytic triad is lowered~~ to ~~allow~~ the ~~nucleophilic attack<ref name="Prom">Branneby, Cecilia. Exploiting Enzyme Promiscuity for Rational Design. KTH Biotechnology. N.p., May 2005</ref>~~. None of the enzymes within the α/β hydrolase fold family require a cofactor for catalytic activity.

The α/β hydrolase fold is common to many other hydrolases <ref name="RSCB"/>. The α/β hydrolase fold has a central 6 stranded parallel β-sheet consisting of <scene name='57/573128/4/1'>β3-β8</scene> and α-helices <scene name='57/573128/5/1'>αA, αB, αC, and αF</scene><ref name="RSCB"/>. A catalytic triad and an oxyanion hole are also common features to the PPT1 protein family. None of the enzymes within the α/β hydrolase fold family require a cofactor for catalytic activity.

=== Catalytic Triad ===

The <scene name='57/573128/2/1'>catalytic triad</scene> is composed of Ser115, His289, and Asp233, which is the same as the catalytic triad in chymotrypsin.

The <scene name='57/573128/2/1'>catalytic triad</scene> is composed of Ser115, His289, and Asp233, which is the same as the catalytic triad in chymotrypsin <ref name="human"/>. A water molecule is occupying the <scene name='57/573128/7/1'>oxyanion hole</scene> and it is hydrogen bonded to Ser115 <ref name="Prom"/>. The purpose of the oxyanion hole is to stabilize the oxyanion that is formed after the nucleophilic attack of the transition state. Ser115 acts as a nucleophile, while His289 and Asp233 are coordinated to Ser115 to lower its pKa value so it can undergo catalytic activity<ref name="Prom"/>. The pKa of the nucleophile in the catalytic triad is lowered to allow the nucleophilic attack<ref name="Prom">Branneby, Cecilia. Exploiting Enzyme Promiscuity for Rational Design. KTH Biotechnology. N.p., May 2005</ref>.

A water molecule is occupying the <scene name='57/573128/7/1'>oxyanion hole</scene> and it is hydrogen bonded to Ser115 <ref name="Prom"/>. The purpose of the oxyanion hole is to stabilize the oxyanion that is formed after the nucleophilic attack~~, which happens to be in~~ the transition state. Ser115 acts as a nucleophile, while His289 and Asp233 are coordinated to Ser115 to lower its pKa value so it can undergo catalytic activity<ref name="Prom"/>.

===Hydrophobic Groove ===

The <scene name='57/573128/3/1'>hydrophobic binding groove</scene> is located in the second domain of PPT1, where palmitate mainly binds. The fact that palmitate has to <scene name='57/573128/6/1'>bend</scene> to fit into the binding pocket suggests that this pocket is designed to bind an unsaturated fatty acid, with a possible cis-double bond between C4 and C5<ref name="RSCB"/>. The top portion of the groove is formed by the residues from α2 to α3. Several residues that are present near the active site create the rest of the groove, including Ile235, Val236, Gln116, Gly40, and Met41<ref name="RSCB"/>.

The <scene name='57/573128/3/1'>hydrophobic binding groove</scene> is located in the second domain of PPT1, where palmitate mainly binds. The fact that palmitate has to <scene name='57/573128/6/1'>bend</scene> to fit into the binding pocket suggests that this pocket is designed to bind an unsaturated fatty acid, with a possible cis-double bond between C4 and C5<ref name="RSCB"/>. The top portion of the groove is formed by the residues from α2 to α3. Several residues that are present near the active site create the rest of the groove, including <scene name='57/573128/10/1'>Ile235, Val236, Gln116, Gly40, and Met41</scene><ref name="RSCB"/>.

== Function ==

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 The secondary structure of PPT1 contains several α-helices and few β-sheets (Figure 1). PPT1 includes residues 28-306, after the 27-residue signal peptide has been removed <ref name="RSCB">Bellizzi III, John. RCSB Protein Data Bank. PNAS, 18 Apr. 2000.</ref>. An insertion is found between β6 and β7, residues 140-223, and that forms a <scene name='57/573128/9/1'>second domain</scene>, shown in blue, that is compromised almost entirely of the fatty acid binding site. This second domain region contains six helices, α2-α7<ref name="RSCB"/>.
-The α/β Hydrolase Fold is common to many other hydrolases. The α/β hydrolase fold has a central 6 stranded parallel β-sheet consisting of <scene name='57/573128/4/1'>β3-β8</scene> and α-helices <scene name='57/573128/5/1'>αA, αB, αC, and αF</scene><ref name="RSCB"/>. It also consists of a catalytic triad and an oxyanion hole. The pKa of the nucleophile in the catalytic triad is lowered to allow the nucleophilic attack<ref name="Prom">Branneby, Cecilia. Exploiting Enzyme Promiscuity for Rational Design. KTH Biotechnology. N.p., May 2005</ref>. None of the enzymes within the α/β hydrolase fold family require a cofactor for catalytic activity.
+The α/β hydrolase fold is common to many other hydrolases <ref name="RSCB"/>. The α/β hydrolase fold has a central 6 stranded parallel β-sheet consisting of <scene name='57/573128/4/1'>β3-β8</scene> and α-helices <scene name='57/573128/5/1'>αA, αB, αC, and αF</scene><ref name="RSCB"/>. A catalytic triad and an oxyanion hole are also common features to the PPT1 protein family. None of the enzymes within the α/β hydrolase fold family require a cofactor for catalytic activity.
 === Catalytic Triad ===
-The <scene name='57/573128/2/1'>catalytic triad</scene> is composed of Ser115, His289, and Asp233, which is the same as the catalytic triad in chymotrypsin.
+The <scene name='57/573128/2/1'>catalytic triad</scene> is composed of Ser115, His289, and Asp233, which is the same as the catalytic triad in chymotrypsin <ref name="human"/>. A water molecule is occupying the <scene name='57/573128/7/1'>oxyanion hole</scene> and it is hydrogen bonded to Ser115 <ref name="Prom"/>. The purpose of the oxyanion hole is to stabilize the oxyanion that is formed after the nucleophilic attack of the transition state. Ser115 acts as a nucleophile, while His289 and Asp233 are coordinated to Ser115 to lower its pKa value so it can undergo catalytic activity<ref name="Prom"/>. The pKa of the nucleophile in the catalytic triad is lowered to allow the nucleophilic attack<ref name="Prom">Branneby, Cecilia. Exploiting Enzyme Promiscuity for Rational Design. KTH Biotechnology. N.p., May 2005</ref>.
-A water molecule is occupying the <scene name='57/573128/7/1'>oxyanion hole</scene> and it is hydrogen bonded to Ser115 <ref name="Prom"/>. The purpose of the oxyanion hole is to stabilize the oxyanion that is formed after the nucleophilic attack, which happens to be in the transition state. Ser115 acts as a nucleophile, while His289 and Asp233 are coordinated to Ser115 to lower its pKa value so it can undergo catalytic activity<ref name="Prom"/>.
 ===Hydrophobic Groove ===
-The <scene name='57/573128/3/1'>hydrophobic binding groove</scene> is located in the second domain of PPT1, where palmitate mainly binds. The fact that palmitate has to <scene name='57/573128/6/1'>bend</scene> to fit into the binding pocket suggests that this pocket is designed to bind an unsaturated fatty acid, with a possible cis-double bond between C4 and C5<ref name="RSCB"/>. The top portion of the groove is formed by the residues from α2 to α3. Several residues that are present near the active site create the rest of the groove, including Ile235, Val236, Gln116, Gly40, and Met41<ref name="RSCB"/>.
+The <scene name='57/573128/3/1'>hydrophobic binding groove</scene> is located in the second domain of PPT1, where palmitate mainly binds. The fact that palmitate has to <scene name='57/573128/6/1'>bend</scene> to fit into the binding pocket suggests that this pocket is designed to bind an unsaturated fatty acid, with a possible cis-double bond between C4 and C5<ref name="RSCB"/>. The top portion of the groove is formed by the residues from α2 to α3. Several residues that are present near the active site create the rest of the groove, including <scene name='57/573128/10/1'>Ile235, Val236, Gln116, Gly40, and Met41</scene><ref name="RSCB"/>.
 == Function ==