Phospholipases: structural and functional motifs for working at an interface.
Phospholipases form a ubiquitous class of enzymes optimized to catalyze the hydrolysis of phospholipids. Because their products are often second messengers, they are highly regulated by the cell. For a given ester bond, there are separate secreted as well as cytoplasmic phospholipases with different substrate specificities and modes of regulation. As it becomes available, structural information provides a view of interfacial catalysis for several of these phospholipases on a molecular level. Recent structural advances include solution structures of a pancreatic phospholipase A2 in the absence and presence of a micellar interface, crystal structures of a bacterial phosphatidylinositol-phospholipase C whose active site is reminiscent of ribonuclease, and a Ca2+ lipid binding domain with high homology to regions in several cytoplasmic phospholipases that can model the way those proteins interact with the membrane surface. Phospholipases also have a wide and complex array of regulatory mechanisms involving cytoplasmic proteins, notably G-proteins, as well as different effector lipids (e.g., phosphatidylinositol-4,5-biphosphate, or PIP2) or Ca2+. Deconvolution of these interactions is necessary to understand their roles in different signal transduction pathways.-Roberts, M. F. Phospholipases: structural and functional motifs for working at an interface.
Roberts
M F
MF
Boston College, Merkert Chemistry Center, Chestnut Hill, Massachusetts 02167, USA.
D000818:Animals; D002118:Calcium / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D010739:Phospholipase D / Q000737:chemistry / Q000502:physiology; D010740:Phospholipases / Q000737:chemistry* / Q000502:physiology*; D010741:Phospholipases A / Q000737:chemistry / Q000502:physiology; D054467:Phospholipases A2; D010738:Type C Phospholipases / Q000737:chemistry / Q000502:physiology
D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases; D010739:Phospholipase D; D019204:GTP-Binding Proteins; D002118:Calcium