4AL0
Crystal structure of Human PS-1
Summary for 4AL0
Entry DOI | 10.2210/pdb4al0/pdb |
Related | 4AL1 |
Descriptor | PROSTAGLANDIN E SYNTHASE, GLUTATHIONE, PALMITIC ACID, ... (5 entities in total) |
Functional Keywords | isomerase, membrane protein, lipid biosynthesis |
Biological source | HOMO SAPIENS (HUMAN) |
Total number of polymer chains | 1 |
Total formula weight | 18784.66 |
Authors | Sjogren, T.,Nord, J.,Ek, M.,Johansson, P.,Liu, G.,Geschwindner, S. (deposition date: 2012-02-29, release date: 2013-02-06, Last modification date: 2024-05-08) |
Primary citation | Sjogren, T.,Nord, J.,Ek, M.,Johansson, P.,Liu, G.,Geschwindner, S. Crystal Structure of Microsomal Prostaglandin E2 Synthase Provides Insight Into Diversity in the Mapeg Superfamily. Proc.Natl.Acad.Sci.USA, 110:3806-, 2013 Cited by PubMed Abstract: Prostaglandin E2 (PGE2) is a key mediator in inflammatory response. The main source of inducible PGE2, microsomal PGE2 synthase-1 (mPGES-1), has emerged as an interesting drug target for treatment of pain. To support inhibitor design, we have determined the crystal structure of human mPGES-1 to 1.2 Å resolution. The structure reveals three well-defined active site cavities within the membrane-spanning region in each monomer interface of the trimeric structure. An important determinant of the active site cavity is a small cytosolic domain inserted between transmembrane helices I and II. This extra domain is not observed in other structures of proteins within the MAPEG (Membrane-Associated Proteins involved in Eicosanoid and Glutathione metabolism) superfamily but is likely to be present also in microsomal GST-1 based on sequence similarity. An unexpected feature of the structure is a 16-Å-deep cone-shaped cavity extending from the cytosolic side into the membrane-spanning region. We suggest a potential role for this cavity in substrate access. Based on the structure of the active site, we propose a catalytic mechanism in which serine 127 plays a key role. We have also determined the structure of mPGES-1 in complex with a glutathione-based analog, providing insight into mPGES-1 flexibility and potential for structure-based drug design. PubMed: 23431194DOI: 10.1073/PNAS.1218504110 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (1.16 Å) |
Structure validation
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