Sandbox89220: Difference between revisions

[[Image:2AMY(1).jpg|300px|left|thumb|Phosphomannose mutase 2,[[2amy]]]] The exploration of one of the inheritance disorders, CDG (Congenital disorder of glycosylation), reveals the fact that having defects in one copy of the genes, we could have a whole spectrum of disorders manifestations in individuals, ranging from mild to severe clinical complications. The protein which comes to the spotlight with the disorder is none of the others but the phosphomannose mutase 2 (PMM2). Since it has the function of shuttling the phosphoryl group, thus converting mannose-6-phosphate into mannose-1-phosphate (the building block for oligosaccharides for glycoproteins), it’s said to closely resemble the function of phosphoglucomutase, that PMMs are known as PGM (phosphoglucomutase) <ref>Chung et al,Domain motion and interdomain hot spots in a multidomain enzyme[http://onlinelibrary.wiley.com/doi/10.1002/pro.446/pdf]</ref>. It’s reasonable to think about PMM2 to work in the same way as phosphoglucomutase does, by changing the phosphorylated position; still, the machinery of how the protein works remains mysterious. Through the exploration of its paralog, PMM1, we could then figure out bits by bits about PMM2’s structure and look at how the protein’s defects could impact on the body systems, evolutionary mutations that cause the difference of its function compared to PMM1, the clinical manifestations, and the potential manipulation of PMM2 in pharmaceutical field in the future. Phosphomannose mutase 2 is an cytosolic enzyme which is critical in the conversion of mannose-6-phosphate into mannose-1-phosphate. It's a homodimeric protein, having two identical subunits working as independent domains. It's a typical HAD superfamily protein, which has the characteristic "cap" and "core" domains.