User:Morgan Bertolino/Sandbox 1
From Proteopedia
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== The HAD Superfamily == | == The HAD Superfamily == | ||
The haloacid dehalogenase superfamily contains over 79,000 unique sequences of enzymes and is largely made up of enzymes that catalyze phosphoryl transfer<ref>DOI: 10.1016/j.bbamcr.2018.07.007</ref>. **Phosphatases** (phosphate monoester hydrolases) make up the majority of these enzymes at ~79%, with many of the rest be **ATPases** (phosphoanhydride hydrolases)<ref>DOI: 10.1111/j.1742-4658.2012.08633.x</ref>. While many members of the enzyme family are found predominantly in prokaryotes, 183 human HAD enzymes have been identified, with at least 40 HAD-type phosphatases. This ancient group of enzymes has evolved over time to dephosphorylate a wide variety of substituents including carbohydrates, lipids, DNA, and various amino acid-phosphorylated proteins in humans, though many target small metabolites in intermediary metabolic reactions. These enzyme were originally thought to carry out simple regulatory tasks, but recent research has shown that some of these enzymes play roles in various genetic disorders<ref>DOI: 10.1016/j.bbamcr.2018.07.007</ref>. | The haloacid dehalogenase superfamily contains over 79,000 unique sequences of enzymes and is largely made up of enzymes that catalyze phosphoryl transfer<ref>DOI: 10.1016/j.bbamcr.2018.07.007</ref>. **Phosphatases** (phosphate monoester hydrolases) make up the majority of these enzymes at ~79%, with many of the rest be **ATPases** (phosphoanhydride hydrolases)<ref>DOI: 10.1111/j.1742-4658.2012.08633.x</ref>. While many members of the enzyme family are found predominantly in prokaryotes, 183 human HAD enzymes have been identified, with at least 40 HAD-type phosphatases. This ancient group of enzymes has evolved over time to dephosphorylate a wide variety of substituents including carbohydrates, lipids, DNA, and various amino acid-phosphorylated proteins in humans, though many target small metabolites in intermediary metabolic reactions. These enzyme were originally thought to carry out simple regulatory tasks, but recent research has shown that some of these enzymes play roles in various genetic disorders<ref>DOI: 10.1016/j.bbamcr.2018.07.007</ref>. | ||
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| + | Sequentially, there is very low similarity across the HAD phosphatases, so members of the family are instead identified using alignments of amino acid sequences that are based on the presence of **four short signature motifs** that contain conserved catalytic residues present in HAD enzymes. Another similarity between the HAD phosphatase superfamily is that all the enzymes share the same active core structural arrangement, consisting of catalytic machinery residues positioned in a **Rossmann fold**. This super-secondary structure is characterized by an alternating motif of repeating β-α units arranged in three stacked α/β sandwiches. The Rossmann fold of HAD phosphatases also contains three unique structural signatures including the **squiggle**, **flap**, and **cap** domains. These domains allow HAD phosphatases to form different conformational states as well as influence substrate specificity<ref>DOI: 10.1111/j.1742-4658.2012.08633.x</ref>. | ||
== HAD Phosphatases: Mechanism & Structure == | == HAD Phosphatases: Mechanism & Structure == | ||
| + | The catalysis mechanism of HAD phosphatases is unique in comparison to other phosphatases and requires the use of an aspartate residue in the active site. This residue facilitates a nucleophilic attack and also contributes to these enzymes' lack of sensitivity to common phosphatase inhibitors. This attack is carried out in a two-step phosphoaspartyl transferase mechanism. | ||
== LHPP-Specific Mechanisms & Structure == | == LHPP-Specific Mechanisms & Structure == | ||
Revision as of 03:50, 23 April 2020
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