User:Morgan Bertolino/Sandbox 1
From Proteopedia
(Difference between revisions)
| Line 4: | Line 4: | ||
== 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 | + | The haloacid dehalogenase superfamily contains over 79,000 unique sequences of enzymes and is largely made up of enzymes that catalyze phosphoryl transfer<ref name=Gohla/>. **Phosphatases** (phosphate monoester hydrolases) make up the majority of these enzymes at ~79%, with many of the rest be **ATPases** (phosphoanhydride hydrolases)<ref name=Seifried/>. 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 name=Gohla/>. |
| - | 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 | + | 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 name=Seifried/>. |
== HAD Phosphatases: Mechanism & Structure == | == HAD Phosphatases: Mechanism & Structure == | ||
Revision as of 03:56, 23 April 2020
Background
| |||||||||||
