5M7F

Human porphobilinogen deaminase in complex with DPM cofactor

5M7F の概要

• エントリーDOI: 10.2210/pdb5m7f/pdb
• 分子名称: Porphobilinogen deaminase, 3-[5-{[3-(2-carboxyethyl)-4-(carboxymethyl)-5-methyl-1H-pyrrol-2-yl]methyl}-4-(carboxymethyl)-1H-pyrrol-3-yl]propanoic acid, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: porphobilinogen deaminase, heme biosynthesis, porphyria, hmbs, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 81987.29

構造登録者

Pluta, P.,Millet, O.,Roversi, P.,Rojas, A.L.,Gu, S. (登録日: 2016-10-27, 公開日: 2017-11-15, 最終更新日: 2024-01-17)

主引用文献

Pluta, P.,Roversi, P.,Bernardo-Seisdedos, G.,Rojas, A.L.,Cooper, J.B.,Gu, S.,Pickersgill, R.W.,Millet, O.
Structural basis of pyrrole polymerization in human porphobilinogen deaminase.
Biochim Biophys Acta Gen Subj, 1862:1948-1955, 2018

PubMed Abstract: Human porphobilinogen deaminase (PBGD), the third enzyme in the heme pathway, catalyzes four times a single reaction to convert porphobilinogen into hydroxymethylbilane. Remarkably, PBGD employs a single active site during the process, with a distinct yet chemically equivalent bond formed each time. The four intermediate complexes of the enzyme have been biochemically validated and they can be isolated but they have never been structurally characterized other than the apo- and holo-enzyme bound to the cofactor. We present crystal structures for two human PBGD intermediates: PBGD loaded with the cofactor and with the reaction intermediate containing two additional substrate pyrrole rings. These results, combined with SAXS and NMR experiments, allow us to propose a mechanism for the reaction progression that requires less structural rearrangements than previously suggested: the enzyme slides a flexible loop over the growing-product active site cavity. The structures and the mechanism proposed for this essential reaction explain how a set of missense mutations result in acute intermittent porphyria.

PubMed: 29908816
DOI: 10.1016/j.bbagen.2018.06.013

実験手法

X-RAY DIFFRACTION (2.78 Å)