Sandbox Reserved 349: Difference between revisions
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Although PBGD appears to have hydrogen bonding capabilities between two identical PBGD units, at physiological pH, these interactions account for a dimer interface of approximately 5% while average dimer interface between subunits is 16%<ref name="Raj">PMID: 19207107</ref>. Therefore, it is generally assumed that this protein is active naturally as a monomeric enzyme, while the crystalline form is a homo-dimeric structure of two identical PBGD subunits<ref name="Raj">PMID: 19207107</ref>. | Although PBGD appears to have hydrogen bonding capabilities between two identical PBGD units, at physiological pH, these interactions account for a dimer interface of approximately 5% while average dimer interface between subunits is 16%<ref name="Raj">PMID: 19207107</ref>. Therefore, it is generally assumed that this protein is active naturally as a monomeric enzyme, while the crystalline form is a homo-dimeric structure of two identical PBGD subunits<ref name="Raj">PMID: 19207107</ref>. | ||
==Mechanism== | ==Mechanism== | ||
PBGD is responsible for the formation of hydroxymethylbilane (HMB) from four porphobilinogen (PBG) subunits<ref name="Peter">PMID:3079571</ref>. The enzyme is loaded with a single porphobilinogen that is covalently linked to the dipyrromethane cofactor<ref name="Lander">PMID: 2025226</ref>. The remaining three PBG units are attached in a head-to-tail fashion to yield an early, linear, HMB precursor that is covalently linked to PBGD<ref name="Lander">PMID: 2025226</ref>. | PBGD is responsible for the formation of hydroxymethylbilane (HMB) from four porphobilinogen (PBG) subunits<ref name="Peter">PMID:3079571</ref>. The enzyme is loaded with a single porphobilinogen that is covalently linked to the dipyrromethane cofactor<ref name="Lander">PMID: 2025226</ref>. The remaining three PBG units are attached in a head-to-tail fashion to yield an early, linear, HMB precursor that is covalently linked to PBGD<ref name="Lander">PMID: 2025226</ref>. The six pyrole unit compound is cleaved at the second pyrole to yield the final product, hydroxymethylbilane<ref> A.R. Battersby, F.J. Leeper. Biosynthesis of the pigments of life: mechanistic studies on the conversion of porphobilinogen to uroporphyrinogen III. Chern. Rev. 1990 Nov;90(7):1261-1274</ref>. | ||
==Importance of hPBGD== | ==Importance of hPBGD== | ||
===Acute Intermittent Porphyria=== | ===Acute Intermittent Porphyria=== | ||
