https://proteopedia.org/api.php?action=feedcontributions&feedformat=atom&user=Mriganki+Sarma 2026-09-18T18:03:59Z User contributions MediaWiki 1.43.8 https://proteopedia.org/index.php?title=PLD3_8V05:_BI3323-Aug2025&diff=4396589 2025-11-30T15:13:28Z

<p>Mriganki Sarma: </p> <hr /> <div>== Introduction ==<br /> Phospholipase D3 (PLD3) is an enzyme found inside endolysosomes, where it helps clear out stray single-stranded DNA and RNA before they can trigger immune alarms. The structure shown here (PDB 8V05) represents the soluble luminal portion of mouse PLD3, which closely reflects the behaviour of human PLD4. <br /> The crystal structure of mouse PLD3 (PDB ID: 8V05) reveals a pseudo-dimeric architecture consisting of two structurally similar domains, Domain A (residues 69–254) and Domain B (residues 277–488), connected by a flexible linker (residues 255–276). Both domains contain β-sheets. In the first image (Overall structure of PLD3 (PDB 8V05)), domain A is marked with green and domain B with orange, with a pink linker bridging them. Their interface is involved in catalysis.<br /> <br /> == Structural highlights ==<br /> PLD3 uses two conserved HKD motifs to break down genetic material. The first motif (H199, K201, D206) lies in Domain A, and the second (H414, K416, E421) sits in Domain B. Together, they build a positively charged pocket that draws in the negatively charged phosphates of DNA/RNA. Evidence from structural studies suggests that H414 performs the key attack on the phosphodiester bond, briefly forming a phosphohistidine intermediate. H199 from Domain A serves as a proton shuttle, facilitates hydrolysis of this intermediate by activating a water molecule, releasing a single 3′-phosphate nucleotide and regenerating the enzyme. PLD3 also exhibits weak phosphatase activity toward 5′-phosphorylated nucleic acids, whereby H414 captures the 5′ phosphate to form the phosphohistidine intermediate, which is subsequently hydrolyzed to release inorganic phosphate. This phosphatase activity inhibits exonuclease function by trapping the enzyme in the covalent intermediate state. The second image (HKD catalytic center of PLD3) highlights the catalytic histidines of HKD1 in blue and HKD2 in red.<br /> <br /> == Significance ==<br /> PLD3 is an endolysosomal nuclease linked to neuronal health and late-onset Alzheimer’s disease. Its dysfunction leads to impaired nucleic-acid clearance and lysosomal stress.<br /> <br /> == References ==<br /> Meng Yuan, Linghang Peng, Deli Huang, Amanda Gavin, Fangkun Luan, Jenny Tran, Ziqi Feng, Xueyong Zhu, Jeanne Matteson, Ian A. Wilson, and David Nemazee, Structural and mechanistic insights into disease-associated endolysosomal exonucleases PLD3 and PLD4<br /> <br /> == 3D Images ==<br /> [[Image:PLD3_overall.png|thumb|400px|Overall structure of PLD3 (PDB 8V05).]]<br /> [[Image:PLD3_active.png|thumb|400px|HKD catalytic center of PLD3.]]<br /> <br /> &lt;Structure load='8V05' size='350' frame='true' align='right' caption='PDL3 (PDB ID: 8V05)' scene='Insert optional scene name here' /&gt;</div>

Mriganki Sarma https://proteopedia.org/index.php?title=PLD3_8V05:_BI3323-Aug2025&diff=4396584 2025-11-30T15:09:38Z

<p>Mriganki Sarma: </p> <hr /> <div>== Introduction ==<br /> Phospholipase D3 (PLD3) is an enzyme found inside endolysosomes, where it helps clear out stray single-stranded DNA and RNA before they can trigger immune alarms. The structure shown here (PDB 8V05) represents the soluble luminal portion of mouse PLD3, which closely reflects the behaviour of human PLD4. <br /> The crystal structure of mouse PLD3 (PDB ID: 8V05) reveals a pseudo-dimeric architecture consisting of two structurally similar domains, Domain A (residues 69–254) and Domain B (residues 277–488), connected by a flexible linker (residues 255–276). Both domains contain β-sheets. In the first image (Overall structure of PLD3 (PDB 8V05)), domain A is marked with green and domain B with orange, with a pink linker bridging them. Their interface is involved in catalysis.<br /> <br /> == Structural highlights ==<br /> PLD3 uses two conserved HKD motifs to break down genetic material. The first motif (H199, K201, D206) lies in Domain A, and the second (H414, K416, E421) sits in Domain B. Together, they build a positively charged pocket that draws in the negatively charged phosphates of DNA/RNA. Evidence from structural studies suggests that H414 performs the key attack on the phosphodiester bond, briefly forming a phosphohistidine intermediate. H199 from Domain A serves as a proton shuttle, facilitates hydrolysis of this intermediate by activating a water molecule, releasing a single 3′-phosphate nucleotide and regenerating the enzyme. PLD3 also exhibits weak phosphatase activity toward 5′-phosphorylated nucleic acids, whereby H414 captures the 5′ phosphate to form the phosphohistidine intermediate, which is subsequently hydrolyzed to release inorganic phosphate. This phosphatase activity inhibits exonuclease function by trapping the enzyme in the covalent intermediate state. The second image (HKD catalytic center of PLD3) highlights the catalytic histidines of HKD1 in blue and HKD2 in red.<br /> <br /> == Significance ==<br /> PLD3 is an endolysosomal nuclease linked to neuronal health and late-onset Alzheimer’s disease. Its dysfunction leads to impaired nucleic-acid clearance and lysosomal stress. The high-resolution structure of PLD3 (8V05) reveals how its HKD motifs assemble into an active nuclease and how substrates are positioned for cleavage. This structural insight helps explain the effects of disease-associated mutations and supports the development of targeted modulators that influence lysosomal function and neurodegeneration.<br /> <br /> == References ==<br /> Meng Yuan, Linghang Peng, Deli Huang, Amanda Gavin, Fangkun Luan, Jenny Tran, Ziqi Feng, Xueyong Zhu, Jeanne Matteson, Ian A. Wilson, and David Nemazee, Structural and mechanistic insights into disease-associated endolysosomal exonucleases PLD3 and PLD4<br /> <br /> == 3D Images ==<br /> [[Image:PLD3_overall.png|thumb|400px|Overall structure of PLD3 (PDB 8V05).]]<br /> [[Image:PLD3_active.png|thumb|400px|HKD catalytic center of PLD3.]]<br /> <br /> &lt;Structure load='8V05' size='350' frame='true' align='right' caption='PDL3 (PDB ID: 8V05)' scene='Insert optional scene name here' /&gt;</div>

Mriganki Sarma https://proteopedia.org/index.php?title=PLD3_8V05:_BI3323-Aug2025&diff=4396583 2025-11-30T15:08:44Z

<p>Mriganki Sarma: </p> <hr /> <div>== Introduction ==<br /> Phospholipase D3 (PLD3) is an enzyme found inside endolysosomes, where it helps clear out stray single-stranded DNA and RNA before they can trigger immune alarms. The structure shown here (PDB 8V05) represents the soluble luminal portion of mouse PLD3, which closely reflects the behaviour of human PLD4. <br /> The crystal structure of mouse PLD3 (PDB ID: 8V05) reveals a pseudo-dimeric architecture consisting of two structurally similar domains, Domain A (residues 69–254) and Domain B (residues 277–488), connected by a flexible linker (residues 255–276). Both domains contain β-sheets. In the first image (Overall structure of PLD3 (PDB 8V05)), domain A is marked with green and domain B with orange, with a pink linker bridging them. Their interface is involved in catalysis.<br /> <br /> == Structural highlights ==<br /> PLD3 uses two conserved HKD motifs to break down genetic material. The first motif (H199, K201, D206) lies in Domain A, and the second (H414, K416, E421) sits in Domain B. Together, they build a positively charged pocket that draws in the negatively charged phosphates of DNA/RNA. Evidence from structural studies suggests that H414 performs the key attack on the phosphodiester bond, briefly forming a phosphohistidine intermediate. H199 from Domain A serves as a proton shuttle, facilitates hydrolysis of this intermediate by activating a water molecule, releasing a single 3′-phosphate nucleotide and regenerating the enzyme. PLD3 also exhibits weak phosphatase activity toward 5′-phosphorylated nucleic acids, whereby H414 captures the 5′ phosphate to form the phosphohistidine intermediate, which is subsequently hydrolyzed to release inorganic phosphate. This phosphatase activity inhibits exonuclease function by trapping the enzyme in the covalent intermediate state. The second image (Active Site) highlights the HKD1 in blue and HKD2 in red.<br /> <br /> == Significance ==<br /> PLD3 is an endolysosomal nuclease linked to neuronal health and late-onset Alzheimer’s disease. Its dysfunction leads to impaired nucleic-acid clearance and lysosomal stress. The high-resolution structure of PLD3 (8V05) reveals how its HKD motifs assemble into an active nuclease and how substrates are positioned for cleavage. This structural insight helps explain the effects of disease-associated mutations and supports the development of targeted modulators that influence lysosomal function and neurodegeneration.<br /> <br /> == References ==<br /> Meng Yuan, Linghang Peng, Deli Huang, Amanda Gavin, Fangkun Luan, Jenny Tran, Ziqi Feng, Xueyong Zhu, Jeanne Matteson, Ian A. Wilson, and David Nemazee, Structural and mechanistic insights into disease-associated endolysosomal exonucleases PLD3 and PLD4<br /> <br /> == 3D Images ==<br /> [[Image:PLD3_overall.png|thumb|400px|Overall structure of PLD3 (PDB 8V05).]]<br /> [[Image:PLD3_active.png|thumb|400px|HKD catalytic center of PLD3.]]<br /> <br /> &lt;Structure load='8V05' size='350' frame='true' align='right' caption='PDL3 (PDB ID: 8V05)' scene='Insert optional scene name here' /&gt;</div>

Mriganki Sarma https://proteopedia.org/index.php?title=PLD3_8V05:_BI3323-Aug2025&diff=4396571 2025-11-30T14:52:01Z

<p>Mriganki Sarma: </p> <hr /> <div>== Introduction ==<br /> Phospholipase D3 (PLD3) is an enzyme found inside endolysosomes, where it helps clear out stray single-stranded DNA and RNA before they can trigger immune alarms. The structure shown here (PDB 8V05) represents the soluble luminal portion of mouse PLD3, which closely reflects the behaviour of human PLD4. <br /> The crystal structure of mouse PLD3 (PDB ID: 8V05) reveals a pseudo-dimeric architecture consisting of two structurally similar domains, Domain A (residues 69–254) and Domain B (residues 277–488), connected by a flexible linker (residues 255–276). Both domains contain β-sheets. In the first image (Overall Structure), domain A is marked with green and domain B with orange, with a pink linker bridging them. Their interface is involved in catalysis.<br /> <br /> == Structural highlights ==<br /> PLD3 uses two conserved HKD motifs to break down genetic material. The first motif (H199, K201, D206) lies in Domain A, and the second (H414, K416, E421) sits in Domain B. Together, they build a positively charged pocket that draws in the negatively charged phosphates of DNA/RNA. Evidence from structural studies suggests that H414 performs the key attack on the phosphodiester bond, briefly forming a phosphohistidine intermediate. H199 from Domain A serves as a proton shuttle, facilitates hydrolysis of this intermediate by activating a water molecule, releasing a single 3′-phosphate nucleotide and regenerating the enzyme. PLD3 also exhibits weak phosphatase activity toward 5′-phosphorylated nucleic acids, whereby H414 captures the 5′ phosphate to form the phosphohistidine intermediate, which is subsequently hydrolyzed to release inorganic phosphate. This phosphatase activity inhibits exonuclease function by trapping the enzyme in the covalent intermediate state. The second image (Active Site) highlights the HKD1 in blue and HKD2 in red.<br /> <br /> == Significance ==<br /> PLD3 is an endolysosomal nuclease linked to neuronal health and late-onset Alzheimer’s disease. Its dysfunction leads to impaired nucleic-acid clearance and lysosomal stress. The high-resolution structure of PLD3 (8V05) reveals how its HKD motifs assemble into an active nuclease and how substrates are positioned for cleavage. This structural insight helps explain the effects of disease-associated mutations and supports the development of targeted modulators that influence lysosomal function and neurodegeneration.<br /> <br /> == References ==<br /> Meng Yuan, Linghang Peng, Deli Huang, Amanda Gavin, Fangkun Luan, Jenny Tran, Ziqi Feng, Xueyong Zhu, Jeanne Matteson, Ian A. Wilson, and David Nemazee, Structural and mechanistic insights into disease-associated endolysosomal exonucleases PLD3 and PLD4<br /> <br /> == 3D Images ==<br /> [[Image:PLD3_overall.png|thumb|400px|Overall structure of PLD3 (PDB 8V05).]]<br /> [[Image:PLD3_active.png|thumb|400px|HKD catalytic center of PLD3.]]<br /> <br /> &lt;Structure load='8V05' size='350' frame='true' align='right' caption='PDL3 (PDB ID: 8V05)' scene='Insert optional scene name here' /&gt;</div>

Mriganki Sarma https://proteopedia.org/index.php?title=PLD3_8V05:_BI3323-Aug2025&diff=4396564 2025-11-30T14:48:17Z

<p>Mriganki Sarma: </p> <hr /> <div>== Introduction ==<br /> Phospholipase D3 (PLD3) is an enzyme found inside endolysosomes, where it helps clear out stray single-stranded DNA and RNA before they can trigger immune alarms. The structure shown here (PDB 8V05) represents the soluble luminal portion of mouse PLD3, which closely reflects the behaviour of human PLD4. <br /> The crystal structure of mouse PLD3 (PDB ID: 8V05) reveals a pseudo-dimeric architecture consisting of two structurally similar domains, Domain A (residues 69–254) and Domain B (residues 277–488), connected by a flexible linker (residues 255–276). Both domains contain β-sheets. In the first image (Overall Structure), domain A is marked with green and domain B with orange, with a pink linker bridging them. Their interface is involved in catalysis.<br /> <br /> == Structural highlights ==<br /> PLD3 uses two conserved HKD motifs to break down genetic material. The first motif (H199, K201, D206) lies in Domain A, and the second (H414, K416, E421) sits in Domain B. Together, they build a positively charged pocket that draws in the negatively charged phosphates of DNA/RNA. Evidence from structural studies suggests that H414 performs the key attack on the phosphodiester bond, briefly forming a phosphohistidine intermediate. H199 from Domain A serves as a proton shuttle, facilitates hydrolysis of this intermediate by activating a water molecule, releasing a single 3′-phosphate nucleotide and regenerating the enzyme. PLD3 also exhibits weak phosphatase activity toward 5′-phosphorylated nucleic acids, whereby H414 captures the 5′ phosphate to form the phosphohistidine intermediate, which is subsequently hydrolyzed to release inorganic phosphate. This phosphatase activity inhibits exonuclease function by trapping the enzyme in the covalent intermediate state. The second image (Active Site) highlights the HKD1 in blue and HKD2 in red.<br /> <br /> == Significance ==<br /> PLD3 is an endolysosomal nuclease linked to neuronal health and late-onset Alzheimer’s disease. Its dysfunction leads to impaired nucleic-acid clearance and lysosomal stress. The high-resolution structure of PLD3 (8V05) reveals how its HKD motifs assemble into an active nuclease and how substrates are positioned for cleavage. This structural insight helps explain the effects of disease-associated mutations and supports the development of targeted modulators that influence lysosomal function and neurodegeneration.<br /> <br /> == References ==<br /> Meng Yuan, Linghang Peng, Deli Huang, Amanda Gavin, Fangkun Luan, Jenny Tran, Ziqi Feng, Xueyong Zhu, Jeanne Matteson, Ian A. Wilson, and David Nemazee, Structural and mechanistic insights into disease-associated endolysosomal exonucleases PLD3 and PLD4<br /> <br /> == 3D Images ==<br /> [[Image:PLD3_overall.png|thumb|400px|Overall structure of PLD3 (PDB 8V05).]]<br /> [[Image:PLD3_active.png|thumb|400px|HKD catalytic center of PLD3.]]<br /> <br /> &lt;Structure load='8V05' size='350' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' /&gt;</div>

Mriganki Sarma https://proteopedia.org/index.php?title=PLD3_8V05&diff=4396563 2025-11-30T14:47:49Z

<p>Mriganki Sarma: PLD3 8V05 moved to PLD3 8V05: BI3323-Aug2025</p> <hr /> <div>#REDIRECT [[PLD3 8V05: BI3323-Aug2025]]</div>

Mriganki Sarma https://proteopedia.org/index.php?title=PLD3_8V05:_BI3323-Aug2025&diff=4396562 2025-11-30T14:47:49Z

<p>Mriganki Sarma: PLD3 8V05 moved to PLD3 8V05: BI3323-Aug2025</p> <hr /> <div>== Introduction ==<br /> Phospholipase D3 (PLD3) is an enzyme found inside endolysosomes, where it helps clear out stray single-stranded DNA and RNA before they can trigger immune alarms. The structure shown here (PDB 8V05) represents the soluble luminal portion of mouse PLD3, which closely reflects the behaviour of human PLD4. <br /> The crystal structure of mouse PLD3 (PDB ID: 8V05) reveals a pseudo-dimeric architecture consisting of two structurally similar domains, Domain A (residues 69–254) and Domain B (residues 277–488), connected by a flexible linker (residues 255–276). Both domains contain β-sheets. In the first image (Overall Structure), domain A is marked with green and domain B with orange, with a pink linker bridging them. Their interface is involved in catalysis.<br /> <br /> == Structural highlights ==<br /> PLD3 uses two conserved HKD motifs to break down genetic material. The first motif (H199, K201, D206) lies in Domain A, and the second (H414, K416, E421) sits in Domain B. Together, they build a positively charged pocket that draws in the negatively charged phosphates of DNA/RNA. Evidence from structural studies suggests that H414 performs the key attack on the phosphodiester bond, briefly forming a phosphohistidine intermediate. H199 from Domain A serves as a proton shuttle, facilitates hydrolysis of this intermediate by activating a water molecule, releasing a single 3′-phosphate nucleotide and regenerating the enzyme. PLD3 also exhibits weak phosphatase activity toward 5′-phosphorylated nucleic acids, whereby H414 captures the 5′ phosphate to form the phosphohistidine intermediate, which is subsequently hydrolyzed to release inorganic phosphate. This phosphatase activity inhibits exonuclease function by trapping the enzyme in the covalent intermediate state. The second image (Active Site) highlights the HKD1 in blue and HKD2 in red.<br /> <br /> == Significance ==<br /> PLD3 is an endolysosomal nuclease linked to neuronal health and late-onset Alzheimer’s disease. Its dysfunction leads to impaired nucleic-acid clearance and lysosomal stress. The high-resolution structure of PLD3 (8V05) reveals how its HKD motifs assemble into an active nuclease and how substrates are positioned for cleavage. This structural insight helps explain the effects of disease-associated mutations and supports the development of targeted modulators that influence lysosomal function and neurodegeneration.<br /> <br /> '''BI3323-Aug2025'''<br /> <br /> <br /> == References ==<br /> Meng Yuan, Linghang Peng, Deli Huang, Amanda Gavin, Fangkun Luan, Jenny Tran, Ziqi Feng, Xueyong Zhu, Jeanne Matteson, Ian A. Wilson, and David Nemazee, Structural and mechanistic insights into disease-associated endolysosomal exonucleases PLD3 and PLD4<br /> <br /> == 3D Images ==<br /> [[Image:PLD3_overall.png|thumb|400px|Overall structure of PLD3 (PDB 8V05).]]<br /> [[Image:PLD3_active.png|thumb|400px|HKD catalytic center of PLD3.]]<br /> <br /> &lt;Structure load='8V05' size='350' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' /&gt;</div>

Mriganki Sarma https://proteopedia.org/index.php?title=PLD3_8V05:_BI3323-Aug2025&diff=4396560 2025-11-30T14:44:58Z

<p>Mriganki Sarma: </p> <hr /> <div>== Introduction ==<br /> Phospholipase D3 (PLD3) is an enzyme found inside endolysosomes, where it helps clear out stray single-stranded DNA and RNA before they can trigger immune alarms. The structure shown here (PDB 8V05) represents the soluble luminal portion of mouse PLD3, which closely reflects the behaviour of human PLD4. <br /> The crystal structure of mouse PLD3 (PDB ID: 8V05) reveals a pseudo-dimeric architecture consisting of two structurally similar domains, Domain A (residues 69–254) and Domain B (residues 277–488), connected by a flexible linker (residues 255–276). Both domains contain β-sheets. In the first image (Overall Structure), domain A is marked with green and domain B with orange, with a pink linker bridging them. Their interface is involved in catalysis.<br /> <br /> == Structural highlights ==<br /> PLD3 uses two conserved HKD motifs to break down genetic material. The first motif (H199, K201, D206) lies in Domain A, and the second (H414, K416, E421) sits in Domain B. Together, they build a positively charged pocket that draws in the negatively charged phosphates of DNA/RNA. Evidence from structural studies suggests that H414 performs the key attack on the phosphodiester bond, briefly forming a phosphohistidine intermediate. H199 from Domain A serves as a proton shuttle, facilitates hydrolysis of this intermediate by activating a water molecule, releasing a single 3′-phosphate nucleotide and regenerating the enzyme. PLD3 also exhibits weak phosphatase activity toward 5′-phosphorylated nucleic acids, whereby H414 captures the 5′ phosphate to form the phosphohistidine intermediate, which is subsequently hydrolyzed to release inorganic phosphate. This phosphatase activity inhibits exonuclease function by trapping the enzyme in the covalent intermediate state. The second image (Active Site) highlights the HKD1 in blue and HKD2 in red.<br /> <br /> == Significance ==<br /> PLD3 is an endolysosomal nuclease linked to neuronal health and late-onset Alzheimer’s disease. Its dysfunction leads to impaired nucleic-acid clearance and lysosomal stress. The high-resolution structure of PLD3 (8V05) reveals how its HKD motifs assemble into an active nuclease and how substrates are positioned for cleavage. This structural insight helps explain the effects of disease-associated mutations and supports the development of targeted modulators that influence lysosomal function and neurodegeneration.<br /> <br /> '''BI3323-Aug2025'''<br /> <br /> <br /> == References ==<br /> Meng Yuan, Linghang Peng, Deli Huang, Amanda Gavin, Fangkun Luan, Jenny Tran, Ziqi Feng, Xueyong Zhu, Jeanne Matteson, Ian A. Wilson, and David Nemazee, Structural and mechanistic insights into disease-associated endolysosomal exonucleases PLD3 and PLD4<br /> <br /> == 3D Images ==<br /> [[Image:PLD3_overall.png|thumb|400px|Overall structure of PLD3 (PDB 8V05).]]<br /> [[Image:PLD3_active.png|thumb|400px|HKD catalytic center of PLD3.]]<br /> <br /> &lt;Structure load='8V05' size='350' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' /&gt;</div>

Mriganki Sarma https://proteopedia.org/index.php?title=PLD3_8V05:_BI3323-Aug2025&diff=4396556 2025-11-30T14:38:45Z

<p>Mriganki Sarma: </p> <hr /> <div>== Introduction ==<br /> Phospholipase D3 (PLD3) is an enzyme found inside endolysosomes, where it helps clear out stray single-stranded DNA and RNA before they can trigger immune alarms. The structure shown here (PDB 8V05) represents the soluble luminal portion of mouse PLD3, which closely reflects the behaviour of human PLD4. <br /> The crystal structure of mouse PLD3 (PDB ID: 8V05) reveals a pseudo-dimeric architecture consisting of two structurally similar domains, Domain A (residues 69–254) and Domain B (residues 277–488), connected by a flexible linker (residues 255–276). Both domains contain β-sheets. In the first image (Overall Structure), domain A is marked with green and domain B with orange, with a pink linker bridging them. Their interface is involved in catalysis.<br /> <br /> == Structural highlights ==<br /> PLD3 uses two conserved HKD motifs to break down genetic material. The first motif (H199, K201, D206) lies in Domain A, and the second (H414, K416, E421) sits in Domain B. Together, they build a positively charged pocket that draws in the negatively charged phosphates of DNA/RNA. Evidence from structural studies suggests that H414 performs the key attack on the phosphodiester bond, briefly forming a phosphohistidine intermediate. H199 from Domain A serves as a proton shuttle, facilitates hydrolysis of this intermediate by activating a water molecule, releasing a single 3′-phosphate nucleotide and regenerating the enzyme. PLD3 also exhibits weak phosphatase activity toward 5′-phosphorylated nucleic acids, whereby H414 captures the 5′ phosphate to form the phosphohistidine intermediate, which is subsequently hydrolyzed to release inorganic phosphate. This phosphatase activity inhibits exonuclease function by trapping the enzyme in the covalent intermediate state. The second image (Active Site) highlights the HKD1 in blue and HKD2 in red.<br /> <br /> == Significance ==<br /> PLD3 is an endolysosomal nuclease linked to neuronal health and late-onset Alzheimer’s disease. Its dysfunction leads to impaired nucleic-acid clearance and lysosomal stress. The high-resolution structure of PLD3 (8V05) reveals how its HKD motifs assemble into an active nuclease and how substrates are positioned for cleavage. This structural insight helps explain the effects of disease-associated mutations and supports the development of targeted modulators that influence lysosomal function and neurodegeneration.<br /> <br /> '''BI3323-Aug2025'''<br /> <br /> <br /> == References ==<br /> Meng Yuan, Linghang Peng, Deli Huang, Amanda Gavin, Fangkun Luan, Jenny Tran, Ziqi Feng, Xueyong Zhu, Jeanne Matteson, Ian A. Wilson, and David Nemazee, Structural and mechanistic insights into disease-associated endolysosomal exonucleases PLD3 and PLD4<br /> <br /> == 3D Images ==<br /> [[Image:PLD3_overall.png|thumb|400px|Overall structure of PLD3 (PDB 8V05).]]<br /> [[Image:PLD3_active.png|thumb|400px|HKD catalytic center of PLD3.]]<br /> <br /> {{3D Structure}}</div>

Mriganki Sarma https://proteopedia.org/index.php?title=PLD3_8V05:_BI3323-Aug2025&diff=4396552 2025-11-30T14:34:09Z

<p>Mriganki Sarma: </p> <hr /> <div>== Introduction ==<br /> Phospholipase D3 (PLD3) is an enzyme found inside endolysosomes, where it helps clear out stray single-stranded DNA and RNA before they can trigger immune alarms. The structure shown here (PDB 8V05) represents the soluble luminal portion of mouse PLD3, which closely reflects the behaviour of human PLD4. <br /> The crystal structure of mouse PLD3 (PDB ID: 8V05) reveals a pseudo-dimeric architecture consisting of two structurally similar domains, Domain A (residues 69–254) and Domain B (residues 277–488), connected by a flexible linker (residues 255–276). Both domains contain β-sheets. In the first image (Overall Structure), domain A is marked with green and domain B with orange, with a pink linker bridging them. Their interface is involved in catalysis.<br /> <br /> == Catalytic site and Mechanism ==<br /> PLD3 uses two conserved HKD motifs to break down genetic material. The first motif (H199, K201, D206) lies in Domain A, and the second (H414, K416, E421) sits in Domain B. Together, they build a positively charged pocket that draws in the negatively charged phosphates of DNA/RNA. Evidence from structural studies suggests that H414 performs the key attack on the phosphodiester bond, briefly forming a phosphohistidine intermediate. H199 from Domain A serves as a proton shuttle, facilitates hydrolysis of this intermediate by activating a water molecule, releasing a single 3′-phosphate nucleotide and regenerating the enzyme. PLD3 also exhibits weak phosphatase activity toward 5′-phosphorylated nucleic acids, whereby H414 captures the 5′ phosphate to form the phosphohistidine intermediate, which is subsequently hydrolyzed to release inorganic phosphate. This phosphatase activity inhibits exonuclease function by trapping the enzyme in the covalent intermediate state. The second image (Active Site) highlights the HKD1 in blue and HKD2 in red.<br /> <br /> == Significance ==<br /> PLD3 is an endolysosomal nuclease linked to neuronal health and late-onset Alzheimer’s disease. Its dysfunction leads to impaired nucleic-acid clearance and lysosomal stress. The high-resolution structure of PLD3 (8V05) reveals how its HKD motifs assemble into an active nuclease and how substrates are positioned for cleavage. This structural insight helps explain the effects of disease-associated mutations and supports the development of targeted modulators that influence lysosomal function and neurodegeneration.<br /> <br /> '''BI3323-Aug2025'''<br /> <br /> <br /> == References ==<br /> Meng Yuan, Linghang Peng, Deli Huang, Amanda Gavin, Fangkun Luan, Jenny Tran, Ziqi Feng, Xueyong Zhu, Jeanne Matteson, Ian A. Wilson, and David Nemazee, Structural and mechanistic insights into disease-associated endolysosomal exonucleases PLD3 and PLD4<br /> <br /> == 3D Images ==<br /> [[Image:PLD3_overall.png|thumb|400px|Overall structure of PLD3 (PDB 8V05).]]<br /> [[Image:PLD3_active.png|thumb|400px|HKD catalytic center of PLD3.]]<br /> <br /> {{3D Structure}}</div>

Mriganki Sarma https://proteopedia.org/index.php?title=User:Mriganki_Sarma/PLD3_8V05&diff=4396540 2025-11-30T14:29:19Z

<p>Mriganki Sarma: User:Mriganki Sarma/PLD3 8V05 moved to PLD3 8V05</p> <hr /> <div>#REDIRECT [[PLD3 8V05]]</div>

Mriganki Sarma https://proteopedia.org/index.php?title=PLD3_8V05:_BI3323-Aug2025&diff=4396539 2025-11-30T14:29:19Z

<p>Mriganki Sarma: User:Mriganki Sarma/PLD3 8V05 moved to PLD3 8V05</p> <hr /> <div>== Introduction ==<br /> Phospholipase D3 (PLD3) is an enzyme found inside endolysosomes, where it helps clear out stray single-stranded DNA and RNA before they can trigger immune alarms. The structure shown here (PDB 8V05) represents the soluble luminal portion of mouse PLD3, which closely reflects the behaviour of human PLD4. <br /> The crystal structure of mouse PLD3 (PDB ID: 8V05) reveals a pseudo-dimeric architecture consisting of two structurally similar domains, Domain A (residues 69–254) and Domain B (residues 277–488), connected by a flexible linker (residues 255–276). Both domains contain β-sheets. In the first image (Overall Structure), domain A is marked with green and domain B with orange, with a pink linker bridging them. Their interface is involved in catalysis.<br /> <br /> == Catalytic site and Mechanism ==<br /> PLD3 uses two conserved HKD motifs to break down genetic material. The first motif (H199, K201, D206) lies in Domain A, and the second (H414, K416, E421) sits in Domain B. Together, they build a positively charged pocket that draws in the negatively charged phosphates of DNA/RNA. Evidence from structural studies suggests that H414 performs the key attack on the phosphodiester bond, briefly forming a phosphohistidine intermediate. H199 from Domain A serves as a proton shuttle, facilitates hydrolysis of this intermediate by activating a water molecule, releasing a single 3′-phosphate nucleotide and regenerating the enzyme. PLD3 also exhibits weak phosphatase activity toward 5′-phosphorylated nucleic acids, whereby H414 captures the 5′ phosphate to form the phosphohistidine intermediate, which is subsequently hydrolyzed to release inorganic phosphate. This phosphatase activity inhibits exonuclease function by trapping the enzyme in the covalent intermediate state. The second image (Active Site) highlights the HKD1 in blue and HKD2 in red.<br /> <br /> == Significance ==<br /> PLD3 is an endolysosomal nuclease linked to neuronal health and late-onset Alzheimer’s disease. Its dysfunction leads to impaired nucleic-acid clearance and lysosomal stress. The high-resolution structure of PLD3 (8V05) reveals how its HKD motifs assemble into an active nuclease and how substrates are positioned for cleavage. This structural insight helps explain the effects of disease-associated mutations and supports the development of targeted modulators that influence lysosomal function and neurodegeneration.<br /> <br /> '''BI3323-Aug2025'''<br /> <br /> == References ==<br /> Meng Yuan, Linghang Peng, Deli Huang, Amanda Gavin, Fangkun Luan, Jenny Tran, Ziqi Feng, Xueyong Zhu, Jeanne Matteson, Ian A. Wilson, and David Nemazee, Structural and mechanistic insights into disease-associated endolysosomal exonucleases PLD3 and PLD4<br /> <br /> == 3D Images ==<br /> [[Image:PLD3_overall.png|thumb|400px|Overall structure of PLD3 (PDB 8V05).]]<br /> [[Image:PLD3_active.png|thumb|400px|HKD catalytic center of PLD3.]]</div>

Mriganki Sarma https://proteopedia.org/index.php?title=PLD3_8V05:_BI3323-Aug2025&diff=4396538 2025-11-30T14:28:38Z

<p>Mriganki Sarma: </p> <hr /> <div>== Introduction ==<br /> Phospholipase D3 (PLD3) is an enzyme found inside endolysosomes, where it helps clear out stray single-stranded DNA and RNA before they can trigger immune alarms. The structure shown here (PDB 8V05) represents the soluble luminal portion of mouse PLD3, which closely reflects the behaviour of human PLD4. <br /> The crystal structure of mouse PLD3 (PDB ID: 8V05) reveals a pseudo-dimeric architecture consisting of two structurally similar domains, Domain A (residues 69–254) and Domain B (residues 277–488), connected by a flexible linker (residues 255–276). Both domains contain β-sheets. In the first image (Overall Structure), domain A is marked with green and domain B with orange, with a pink linker bridging them. Their interface is involved in catalysis.<br /> <br /> == Catalytic site and Mechanism ==<br /> PLD3 uses two conserved HKD motifs to break down genetic material. The first motif (H199, K201, D206) lies in Domain A, and the second (H414, K416, E421) sits in Domain B. Together, they build a positively charged pocket that draws in the negatively charged phosphates of DNA/RNA. Evidence from structural studies suggests that H414 performs the key attack on the phosphodiester bond, briefly forming a phosphohistidine intermediate. H199 from Domain A serves as a proton shuttle, facilitates hydrolysis of this intermediate by activating a water molecule, releasing a single 3′-phosphate nucleotide and regenerating the enzyme. PLD3 also exhibits weak phosphatase activity toward 5′-phosphorylated nucleic acids, whereby H414 captures the 5′ phosphate to form the phosphohistidine intermediate, which is subsequently hydrolyzed to release inorganic phosphate. This phosphatase activity inhibits exonuclease function by trapping the enzyme in the covalent intermediate state. The second image (Active Site) highlights the HKD1 in blue and HKD2 in red.<br /> <br /> == Significance ==<br /> PLD3 is an endolysosomal nuclease linked to neuronal health and late-onset Alzheimer’s disease. Its dysfunction leads to impaired nucleic-acid clearance and lysosomal stress. The high-resolution structure of PLD3 (8V05) reveals how its HKD motifs assemble into an active nuclease and how substrates are positioned for cleavage. This structural insight helps explain the effects of disease-associated mutations and supports the development of targeted modulators that influence lysosomal function and neurodegeneration.<br /> <br /> '''BI3323-Aug2025'''<br /> <br /> == References ==<br /> Meng Yuan, Linghang Peng, Deli Huang, Amanda Gavin, Fangkun Luan, Jenny Tran, Ziqi Feng, Xueyong Zhu, Jeanne Matteson, Ian A. Wilson, and David Nemazee, Structural and mechanistic insights into disease-associated endolysosomal exonucleases PLD3 and PLD4<br /> <br /> == 3D Images ==<br /> [[Image:PLD3_overall.png|thumb|400px|Overall structure of PLD3 (PDB 8V05).]]<br /> [[Image:PLD3_active.png|thumb|400px|HKD catalytic center of PLD3.]]</div>

Mriganki Sarma https://proteopedia.org/index.php?title=PLD3_8V05:_BI3323-Aug2025&diff=4396533 2025-11-30T14:22:21Z

<p>Mriganki Sarma: </p> <hr /> <div>== Introduction ==<br /> Phospholipase D3 (PLD3) is an enzyme found inside endolysosomes, where it helps clear out stray single-stranded DNA and RNA before they can trigger immune alarms. The structure shown here (PDB 8V05) represents the soluble luminal portion of mouse PLD3, which closely reflects the behaviour of human PLD4. <br /> The crystal structure of mouse PLD3 (PDB ID: 8V05) reveals a pseudo-dimeric architecture consisting of two structurally similar domains, Domain A (residues 69–254) and Domain B (residues 277–488), connected by a flexible linker (residues 255–276). Both domains contain β-sheets. In the first image (Overall Structure), domain A is marked with green and domain B with orange, with a pink linker bridging them. Their interface is involved in catalysis.<br /> <br /> == Catalytic site and Mechanism ==<br /> PLD3 uses two conserved HKD motifs to break down genetic material. The first motif (H199, K201, D206) lies in Domain A, and the second (H414, K416, E421) sits in Domain B. Together, they build a positively charged pocket that draws in the negatively charged phosphates of DNA/RNA. Evidence from structural studies suggests that H414 performs the key attack on the phosphodiester bond, briefly forming a phosphohistidine intermediate. H199 from Domain A serves as a proton shuttle, facilitates hydrolysis of this intermediate by activating a water molecule, releasing a single 3′-phosphate nucleotide and regenerating the enzyme. PLD3 also exhibits weak phosphatase activity toward 5′-phosphorylated nucleic acids, whereby H414 captures the 5′ phosphate to form the phosphohistidine intermediate, which is subsequently hydrolyzed to release inorganic phosphate. This phosphatase activity inhibits exonuclease function by trapping the enzyme in the covalent intermediate state. The second image (Active Site) highlights the HKD1 in blue and HKD2 in red.<br /> <br /> == Significance ==<br /> PLD3 is an endolysosomal nuclease linked to neuronal health and late-onset Alzheimer’s disease. Its dysfunction leads to impaired nucleic-acid clearance and lysosomal stress. The high-resolution structure of PLD3 (8V05) reveals how its HKD motifs assemble into an active nuclease and how substrates are positioned for cleavage. This structural insight helps explain the effects of disease-associated mutations and supports the development of targeted modulators that influence lysosomal function and neurodegeneration.<br /> <br /> '''BI3323-Aug2025'''<br /> <br /> == References ==<br /> Meng Yuan,1,5,* Linghang Peng,2,5 Deli Huang,2,4,5 Amanda Gavin,2 Fangkun Luan,2 Jenny Tran,2 Ziqi Feng,1 Xueyong Zhu,1 Jeanne Matteson,1 Ian A. Wilson,1,3,* and David Nemazee2,6, Structural and mechanistic insights into disease-associated endolysosomal exonucleases PLD3 and PLD4<br /> <br /> == 3D Images ==<br /> [[Image:PLD3_overall.png|thumb|400px|Overall structure of PLD3 (PDB 8V05).]]<br /> [[Image:PLD3_active.png|thumb|400px|HKD catalytic center of PLD3.]]</div>

Mriganki Sarma https://proteopedia.org/index.php?title=PLD3_8V05:_BI3323-Aug2025&diff=4396524 2025-11-30T14:18:00Z

<p>Mriganki Sarma: </p> <hr /> <div>== Introduction ==<br /> Phospholipase D3 (PLD3) is an enzyme found inside endolysosomes, where it helps clear out stray single-stranded DNA and RNA before they can trigger immune alarms. The structure shown here (PDB 8V05) represents the soluble luminal portion of mouse PLD3, which closely reflects the behaviour of human PLD4. <br /> The crystal structure of mouse PLD3 (PDB ID: 8V05) reveals a pseudo-dimeric architecture consisting of two structurally similar domains, Domain A (residues 69–254) and Domain B (residues 277–488), connected by a flexible linker (residues 255–276). Both domains contain β-sheets. In the first image (Overall Structure), domain A is marked with green and domain B with orange, with a pink linker bridging them. Their interface is involved in catalysis.<br /> <br /> == Catalytic site and Mechanism ==<br /> PLD3 uses two conserved HKD motifs to break down genetic material. The first motif (H199, K201, D206) lies in Domain A, and the second (H414, K416, E421) sits in Domain B. Together, they build a positively charged pocket that draws in the negatively charged phosphates of DNA/RNA. Evidence from structural studies suggests that H414 performs the key attack on the phosphodiester bond, briefly forming a phosphohistidine intermediate. H199 from Domain A serves as a proton shuttle, facilitates hydrolysis of this intermediate by activating a water molecule, releasing a single 3′-phosphate nucleotide and regenerating the enzyme. PLD3 also exhibits weak phosphatase activity toward 5′-phosphorylated nucleic acids, whereby H414 captures the 5′ phosphate to form the phosphohistidine intermediate, which is subsequently hydrolyzed to release inorganic phosphate. This phosphatase activity inhibits exonuclease function by trapping the enzyme in the covalent intermediate state. The second image (Active Site) highlights the HKD1 in blue and HKD2 in red.<br /> Mutations that weaken PLD3’s structure or activity are linked to inflammatory and neurodegenerative disorders.<br /> <br /> == Significance ==<br /> PLD3 is an endolysosomal nuclease linked to neuronal health and late-onset Alzheimer’s disease. Its dysfunction leads to impaired nucleic-acid clearance and lysosomal stress. The high-resolution structure of PLD3 (8V05) reveals how its HKD motifs assemble into an active nuclease and how substrates are positioned for cleavage. This structural insight helps explain the effects of disease-associated mutations and supports the development of targeted modulators that influence lysosomal function and neurodegeneration.<br /> <br /> '''BI3323-Aug2025'''<br /> <br /> == References ==<br /> Meng Yuan,1,5,* Linghang Peng,2,5 Deli Huang,2,4,5 Amanda Gavin,2 Fangkun Luan,2 Jenny Tran,2 Ziqi Feng,1 Xueyong Zhu,1 Jeanne Matteson,1 Ian A. Wilson,1,3,* and David Nemazee2,6, Structural and mechanistic insights into disease-associated endolysosomal exonucleases PLD3 and PLD4<br /> <br /> == 3D Images ==<br /> [[Image:PLD3_overall.png|thumb|400px|Overall structure of PLD3 (PDB 8V05).]]<br /> [[Image:PLD3_active.png|thumb|400px|HKD catalytic center of PLD3.]]</div>

Mriganki Sarma https://proteopedia.org/index.php?title=PLD3_8V05:_BI3323-Aug2025&diff=4396503 2025-11-30T14:06:00Z

<p>Mriganki Sarma: </p> <hr /> <div>== Summary ==<br /> Phospholipase D3 (PLD3) is an enzyme found inside endolysosomes, where it helps clear out stray single-stranded DNA and RNA before they can trigger immune alarms. The structure shown here (PDB 8V05) represents the soluble luminal portion of mouse PLD3, which closely reflects the behaviour of human PLD4. <br /> The crystal structure of mouse PLD3 (PDB ID: 8V05) reveals a pseudo-dimeric architecture consisting of two structurally similar domains, Domain A (residues 69–254) and Domain B (residues 277–488), connected by a flexible linker (residues 255–276). Both domains contain β-sheets. In the first image (Overall Structure), domain A is marked with green and domain B with orange, with a pink linker bridging them. Their interface is involved in catalysis.<br /> PLD3 uses two conserved HKD motifs to break down genetic material. The first motif (H199, K201, D206) lies in Domain A, and the second (H414, K416, E421) sits in Domain B. Together, they build a positively charged pocket that draws in the negatively charged phosphates of DNA/RNA. Evidence from structural studies suggests that H414 performs the key attack on the phosphodiester bond, briefly forming a phosphohistidine intermediate. H199 from Domain A serves as a proton shuttle, facilitates hydrolysis of this intermediate by activating a water molecule, releasing a single 3′-phosphate nucleotide and regenerating the enzyme. PLD3 also exhibits weak phosphatase activity toward 5′-phosphorylated nucleic acids, whereby H414 captures the 5′ phosphate to form the phosphohistidine intermediate, which is subsequently hydrolyzed to release inorganic phosphate. This phosphatase activity inhibits exonuclease function by trapping the enzyme in the covalent intermediate state. The second image (Active Site) highlights the HKD1 in blue and HKD2 in red.<br /> Mutations that weaken PLD3’s structure or activity are linked to inflammatory and neurodegenerative disorders.<br /> <br /> <br /> '''BI3323-Aug2025'''<br /> <br /> == Significance ==<br /> PLD3 is an endolysosomal nuclease linked to neuronal health and late-onset Alzheimer’s disease. Its dysfunction leads to impaired nucleic-acid clearance and lysosomal stress. The high-resolution structure of PLD3 (8V05) reveals how its HKD motifs assemble into an active nuclease and how substrates are positioned for cleavage. This structural insight helps explain the effects of disease-associated mutations and supports the development of targeted modulators that influence lysosomal function and neurodegeneration.<br /> <br /> == References ==<br /> Meng Yuan,1,5,* Linghang Peng,2,5 Deli Huang,2,4,5 Amanda Gavin,2 Fangkun Luan,2 Jenny Tran,2 Ziqi Feng,1 Xueyong Zhu,1 Jeanne Matteson,1 Ian A. Wilson,1,3,* and David Nemazee2,6, Structural and mechanistic insights into disease-associated endolysosomal exonucleases PLD3 and PLD4<br /> <br /> == 3D Images ==<br /> [[Image:PLD3_overall.png|thumb|400px|Overall structure of PLD3 (PDB 8V05).]]<br /> [[Image:PLD3_active.png|thumb|400px|HKD catalytic center of PLD3.]]</div>

Mriganki Sarma https://proteopedia.org/index.php?title=PLD3_8V05:_BI3323-Aug2025&diff=4396485 2025-11-30T13:50:24Z

<p>Mriganki Sarma: </p> <hr /> <div>== Summary ==<br /> Phospholipase D3 (PLD3) is an enzyme found inside endolysosomes, where it helps clear out stray single-stranded DNA and RNA before they can trigger immune alarms. The structure shown here (PDB 8V05) represents the soluble luminal portion of mouse PLD3, which closely reflects the behaviour of human PLD4. <br /> The crystal structure of mouse PLD3 (PDB ID: 8V05) reveals a pseudo-dimeric architecture consisting of two structurally similar domains, Domain A (residues 69–254) and Domain B (residues 277–488), connected by a flexible linker (residues 255–276). Both domains contain β-sheets. In the first image (Overall Structure), domain A is marked with green and domain B with orange, with a pink linker bridging them. Their interface is involved in catalysis.<br /> PLD3 uses two conserved HKD motifs to break down genetic material. The first motif (H199, K201, D206) lies in Domain A, and the second (H414, K416, E421) sits in Domain B. Together, they build a positively charged pocket that draws in the negatively charged phosphates of DNA/RNA. Evidence from structural studies suggests that H414 performs the key attack on the phosphodiester bond, briefly forming a phosphohistidine intermediate. H199 from Domain A serves as a proton shuttle, facilitates hydrolysis of this intermediate by activating a water molecule, releasing a single 3′-phosphate nucleotide and regenerating the enzyme. PLD3 also exhibits weak phosphatase activity toward 5′-phosphorylated nucleic acids, whereby H414 captures the 5′ phosphate to form the phosphohistidine intermediate, which is subsequently hydrolyzed to release inorganic phosphate. This phosphatase activity inhibits exonuclease function by trapping the enzyme in the covalent intermediate state. The second image (Active Site) highlights the HKD1 in blue and HKD2 in red.<br /> Mutations that weaken PLD3’s structure or activity are linked to inflammatory and neurodegenerative disorders.<br /> <br /> == Significance ==<br /> PLD3 is an endolysosomal nuclease linked to neuronal health and late-onset Alzheimer’s disease. Its dysfunction leads to impaired nucleic-acid clearance and lysosomal stress. The high-resolution structure of PLD3 (8V05) reveals how its HKD motifs assemble into an active nuclease and how substrates are positioned for cleavage. This structural insight helps explain the effects of disease-associated mutations and supports the development of targeted modulators that influence lysosomal function and neurodegeneration.<br /> <br /> '''BI3323-Aug2025'''<br /> <br /> == References ==<br /> Structural and mechanistic insights into disease-associated endolysosomal exonucleases PLD3 and PLD4, Meng Yuan,1,5,* Linghang Peng,2,5 Deli Huang,2,4,5 Amanda Gavin,2 Fangkun Luan,2 Jenny Tran,2 Ziqi Feng,1 Xueyong Zhu,1 Jeanne Matteson,1 Ian A. Wilson,1,3,* and David Nemazee2,6,*<br /> <br /> == 3D Images ==<br /> [[Image:PLD3_overall.png|thumb|400px|Overall structure of PLD3 (PDB 8V05).]]<br /> [[Image:PLD3_active.png|thumb|400px|HKD catalytic center of PLD3.]]</div>

Mriganki Sarma https://proteopedia.org/index.php?title=PLD3_8V05:_BI3323-Aug2025&diff=4396477 2025-11-30T13:43:52Z

<p>Mriganki Sarma: </p> <hr /> <div>== Summary ==<br /> Phospholipase D3 (PLD3) is an enzyme found inside endolysosomes, where it helps clear out stray single-stranded DNA and RNA before they can trigger immune alarms. The structure shown here (PDB 8V05) represents the soluble luminal portion of mouse PLD3, which closely reflects the behaviour of human PLD4. <br /> The crystal structure of mouse PLD3 (PDB ID: 8V05) reveals a pseudo-dimeric architecture consisting of two structurally similar domains, Domain A (residues 69–254) and Domain B (residues 277–488), connected by a flexible linker (residues 255–276). Both domains contain β-sheets. In the first image (Overall Structure), domain A is marked with green and domain B with orange, with a pink linker bridging them. Their interface is involved in catalysis.<br /> PLD3 uses two conserved HKD motifs to break down genetic material. The first motif (H199, K201, D206) lies in Domain A, and the second (H414, K416, E421) sits in Domain B. Together, they build a positively charged pocket that draws in the negatively charged phosphates of DNA/RNA. Evidence from structural studies suggests that H414 performs the key attack on the phosphodiester bond, briefly forming a phosphohistidine intermediate. H199 from Domain A serves as a proton shuttle, facilitates hydrolysis of this intermediate by activating a water molecule, releasing a single 3′-phosphate nucleotide and regenerating the enzyme. PLD3 also exhibits weak phosphatase activity toward 5′-phosphorylated nucleic acids, whereby H414 captures the 5′ phosphate to form the phosphohistidine intermediate, which is subsequently hydrolyzed to release inorganic phosphate. This phosphatase activity inhibits exonuclease function by trapping the enzyme in the covalent intermediate state. The second image (Active Site) highlights the HKD1 in blue and HKD2 in red.<br /> Mutations that weaken PLD3’s structure or activity are linked to inflammatory and neurodegenerative disorders.<br /> <br /> '''BI3323-Aug2025'''<br /> <br /> == 3D Images ==<br /> [[Image:PLD3_overall.png|thumb|400px|Overall structure of PLD3 (PDB 8V05).]]<br /> [[Image:PLD3_active.png|thumb|400px|HKD catalytic center of PLD3.]]</div>

Mriganki Sarma https://proteopedia.org/index.php?title=PLD3_8V05:_BI3323-Aug2025&diff=4396464 2025-11-30T13:33:14Z

<p>Mriganki Sarma: </p> <hr /> <div>== Summary ==<br /> Phospholipase D3 (PLD3) is an enzyme found inside endolysosomes, where it helps clear out stray single-stranded DNA and RNA before they can trigger immune alarms. The structure shown here (PDB 8V05) represents the soluble luminal portion of mouse PLD3, which closely reflects the behaviour of human PLD4. <br /> The crystal structure of mouse PLD3 (PDB ID: 8V05) reveals a pseudo-dimeric architecture consisting of two structurally similar domains, Domain A (residues 69–254) and Domain B (residues 277–488), connected by a flexible linker (residues 255–276). Both domains contain β-sheets. In the first image (Overall Structure), domain A is marked with green and domain B with orange, with a pink linker bridging them. Their interface is involved in catalysis.<br /> PLD3 uses two conserved HKD motifs to break down genetic material. The first motif (H199, K201, D206) lies in Domain A, and the second (H414, K416, E421) sits in Domain B. Together, they build a positively charged pocket that draws in the negatively charged phosphates of DNA/RNA. Evidence from structural studies suggests that H414 performs the key attack on the phosphodiester bond, briefly forming a phosphohistidine intermediate. H199 from Domain A serves as a proton shuttle, facilitates hydrolysis of this intermediate by activating a water molecule, releasing a single 3′-phosphate nucleotide and regenerating the enzyme. PLD3 also exhibits weak phosphatase activity toward 5′-phosphorylated nucleic acids, whereby H414 captures the 5′ phosphate to form the phosphohistidine intermediate, which is subsequently hydrolyzed to release inorganic phosphate. This phosphatase activity inhibits exonuclease function by trapping the enzyme in the covalent intermediate state. The second image (Active Site) highlights the HKD1 in blue and HKD2 in red.<br /> Mutations that weaken PLD3’s structure or activity are linked to inflammatory and neurodegenerative disorders.<br /> <br /> '''BI3323-Aug2025'''<br /> <br /> == 3D Scenes ==<br /> {{Mrignaki_PLD3_8V05:Overall_Structure}}<br /> {{Mrignaki_PLD3_8V05:Active_Site}}<br /> <br /> == 3D Images ==<br /> [[Image:PLD3_overall.png|thumb|400px|Overall structure of PLD3 (PDB 8V05).]]<br /> [[Image:PLD3_active.png|thumb|400px|HKD catalytic center of PLD3.]]<br /> <br /> == Scripts ==<br /> &lt;pre&gt;<br /> For the overall structure:<br /> load https://files.rcsb.org/download/8V05.pdb<br /> <br /> # Display the entire protein as ribbon structure<br /> select protein<br /> cartoon on<br /> <br /> # Explicitly hide sticks for all protein residues to ensure no sticks appear in domain regions<br /> select protein<br /> hide sticks<br /> <br /> # Color the domains<br /> select 69-254<br /> color green<br /> select 277-488<br /> color orange<br /> select 255-276<br /> color pink<br /> <br /> # Show ball-and-stick representation ONLY for the active site residues<br /> select 199,201,206,414,416,421<br /> show sticks<br /> spacefill 100%<br /> <br /> # Color the active site residues to distinguish which domain they belong to<br /> select 199,201,206<br /> color blue<br /> <br /> select 414,416,421<br /> color red<br /> <br /> # Add labels to the most important catalytic histidines<br /> select 199<br /> label &quot;H199&quot; <br /> <br /> # Set all labels to white for better visibility<br /> color labels white<br /> <br /> select 414<br /> label &quot;H414&quot;<br /> <br /> # Set all labels to white for better visibility<br /> color labels white<br /> <br /> # Center the view on the active site<br /> center 199,414<br /> zoom 120<br /> <br /> For the active sites only:<br /> <br /> load https://files.rcsb.org/download/8V05.pdb<br /> <br /> # Explicitly show the protein first, then selectively hide other regions<br /> show protein<br /> <br /> # Hide everything except the regions containing the catalytic sites<br /> hide not (190-220 or 405-435)<br /> <br /> # Show the selected regions as sticks<br /> select 190-220 or 405-435<br /> show sticks<br /> <br /> # Make the key catalytic residues more prominent with larger spheres<br /> select 199, 201, 206, 414, 416, 421<br /> spacefill 150%<br /> <br /> # Color the catalytic residues from the two HKD motifs differently<br /> select 199, 201, 206<br /> color blue<br /> <br /> select 414, 416, 421<br /> color red<br /> <br /> # Add labels to the key catalytic histidines<br /> select 199<br /> label &quot;H199&quot;<br /> <br /> # Set all labels to white for better visibility<br /> color labels white<br /> <br /> <br /> select 414<br /> label &quot;H414&quot;<br /> <br /> # Set all labels to white for better visibility<br /> color labels white<br /> <br /> # Center the view on the active site<br /> center 199, 414<br /> zoom 120<br /> &lt;/pre&gt;</div>

Mriganki Sarma https://proteopedia.org/index.php?title=File:PLD3_active.png&diff=4396461 2025-11-30T13:31:09Z

<p>Mriganki Sarma: </p> <hr /> <div></div>

Mriganki Sarma https://proteopedia.org/index.php?title=Mriganki_PLD3_8V05&diff=4396339 2025-11-30T12:05:28Z

<p>Mriganki Sarma: Mriganki PLD3 8V05 moved to User:Mriganki Sarma/PLD3 8V05</p> <hr /> <div>#REDIRECT [[User:Mriganki Sarma/PLD3 8V05]]</div>

Mriganki Sarma https://proteopedia.org/index.php?title=PLD3_8V05:_BI3323-Aug2025&diff=4396338 2025-11-30T12:05:28Z

<p>Mriganki Sarma: Mriganki PLD3 8V05 moved to User:Mriganki Sarma/PLD3 8V05</p> <hr /> <div>== 3D Scenes ==<br /> &lt;!-- Scenes will appear here --&gt;<br /> {{Mriganki_PLD3_8V05:Overall_Structure}}<br /> {{Mriganki_PLD3_8V05:Active_Site}}<br /> <br /> == 3D Images ==<br /> [[Image:PLD3_overall.png|thumb|400px|Overall structure of PLD3 (PDB 8V05).]]<br /> <br /> [[Image:PLD3_active_site.png|thumb|400px|Active site of PLD3 showing catalytic motifs.]]<br /> <br /> <br /> <br /> == Scripts ==<br /> &lt;pre&gt;<br /> (TBD)<br /> &lt;/pre&gt;<br /> &lt;Structure load='8V05' size='350' frame='true' align='right'<br /> caption='Overall structure of PLD3 (PDB 8V05)'<br /> scene='' /&gt;</div>

Mriganki Sarma https://proteopedia.org/index.php?title=PLD3_8V05:_BI3323-Aug2025&diff=4396224 2025-11-30T09:51:42Z

<p>Mriganki Sarma: </p> <hr /> <div>== 3D Scenes ==<br /> &lt;!-- Scenes will appear here --&gt;<br /> {{Mriganki_PLD3_8V05:Overall_Structure}}<br /> {{Mriganki_PLD3_8V05:Active_Site}}<br /> <br /> == 3D Images ==<br /> [[Image:PLD3_overall.png|thumb|400px|Overall structure of PLD3 (PDB 8V05).]]<br /> <br /> [[Image:PLD3_active_site.png|thumb|400px|Active site of PLD3 showing catalytic motifs.]]<br /> <br /> <br /> <br /> == Scripts ==<br /> &lt;pre&gt;<br /> (TBD)<br /> &lt;/pre&gt;<br /> &lt;Structure load='8V05' size='350' frame='true' align='right'<br /> caption='Overall structure of PLD3 (PDB 8V05)'<br /> scene='' /&gt;</div>

Mriganki Sarma https://proteopedia.org/index.php?title=File:PLD3_active_site.png&diff=4396221 2025-11-30T09:50:19Z

<p>Mriganki Sarma: </p> <hr /> <div></div>

Mriganki Sarma https://proteopedia.org/index.php?title=PLD3_8V05:_BI3323-Aug2025&diff=4396214 2025-11-30T09:44:20Z

<p>Mriganki Sarma: </p> <hr /> <div>== 3D Scenes ==<br /> &lt;!-- Scenes will appear here --&gt;<br /> {{Mriganki_PLD3_8V05:Overall_Structure}}<br /> {{Mriganki_PLD3_8V05:Active_Site}}<br /> <br /> == 3D Images ==<br /> [[Image:PLD3_overall.png|thumb|400px|Overall structure of PLD3 (PDB 8V05).]]<br /> <br /> == Scripts ==<br /> &lt;pre&gt;<br /> (TBD)<br /> &lt;/pre&gt;<br /> &lt;Structure load='8V05' size='350' frame='true' align='right'<br /> caption='Overall structure of PLD3 (PDB 8V05)'<br /> scene='' /&gt;</div>

Mriganki Sarma https://proteopedia.org/index.php?title=File:PLD3_overall.png&diff=4396203 2025-11-30T09:31:16Z

<p>Mriganki Sarma: </p> <hr /> <div></div>

Mriganki Sarma https://proteopedia.org/index.php?title=PLD3_8V05:_BI3323-Aug2025&diff=4396190 2025-11-30T08:56:33Z

<p>Mriganki Sarma: New page: == Summary == (TBD) == 3D Scenes == &lt;!-- Scenes will appear here --&gt; {{Mriganki_PLD3_8V05:Overall_Structure}} {{Mriganki_PLD3_8V05:Active_Site}} == Scripts == &lt;pre&gt; (TBD) &lt;/pre&gt; &lt;Structu...</p> <hr /> <div>== Summary ==<br /> (TBD)<br /> <br /> == 3D Scenes ==<br /> &lt;!-- Scenes will appear here --&gt;<br /> {{Mriganki_PLD3_8V05:Overall_Structure}}<br /> {{Mriganki_PLD3_8V05:Active_Site}}<br /> <br /> == Scripts ==<br /> &lt;pre&gt;<br /> (TBD)<br /> &lt;/pre&gt;<br /> &lt;Structure load='8V05' size='350' frame='true' align='right'<br /> caption='Overall structure of PLD3 (PDB 8V05)'<br /> scene='' /&gt;</div>

Mriganki Sarma