2PV7

Crystal structure of chorismate mutase / prephenate dehydrogenase (tyrA) (1574749) from Haemophilus influenzae RD at 2.00 A resolution

2PV7 の概要

• エントリーDOI: 10.2210/pdb2pv7/pdb
• 分子名称: T-protein [Includes: Chorismate mutase (EC 5.4.99.5) (CM) and Prephenate dehydrogenase (EC 1.3.1.12) (PDH)], TYROSINE, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (4 entities in total)
• 機能のキーワード: 1574749, chorismate mutase type ii, chorismate mutase / prephenate dehydrogenase (tyra), structural genomics, joint center for structural genomics, jcsg, protein structure initiative, psi-2, isomerase, oxidoreductase
• 由来する生物種: Haemophilus influenzae
• 細胞内の位置: Cytoplasm: P43902
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 70240.84

構造登録者

Joint Center for Structural Genomics (JCSG) (登録日: 2007-05-09, 公開日: 2007-05-22, 最終更新日: 2024-11-20)

主引用文献

Chiu, H.J.,Abdubek, P.,Astakhova, T.,Axelrod, H.L.,Carlton, D.,Clayton, T.,Das, D.,Deller, M.C.,Duan, L.,Feuerhelm, J.,Grant, J.C.,Grzechnik, A.,Han, G.W.,Jaroszewski, L.,Jin, K.K.,Klock, H.E.,Knuth, M.W.,Kozbial, P.,Krishna, S.S.,Kumar, A.,Marciano, D.,McMullan, D.,Miller, M.D.,Morse, A.T.,Nigoghossian, E.,Okach, L.,Reyes, R.,Tien, H.J.,Trame, C.B.,van den Bedem, H.,Weekes, D.,Xu, Q.,Hodgson, K.O.,Wooley, J.,Elsliger, M.A.,Deacon, A.M.,Godzik, A.,Lesley, S.A.,Wilson, I.A.
The structure of Haemophilus influenzae prephenate dehydrogenase suggests unique features of bifunctional TyrA enzymes.
Acta Crystallogr.,Sect.F, 66:1317-1325, 2010

PubMed Abstract: Chorismate mutase/prephenate dehydrogenase from Haemophilus influenzae Rd KW20 is a bifunctional enzyme that catalyzes the rearrangement of chorismate to prephenate and the NAD(P)(+)-dependent oxidative decarboxylation of prephenate to 4-hydroxyphenylpyruvate in tyrosine biosynthesis. The crystal structure of the prephenate dehydrogenase component (HinfPDH) of the TyrA protein from H. influenzae Rd KW20 in complex with the inhibitor tyrosine and cofactor NAD(+) has been determined to 2.0 Å resolution. HinfPDH is a dimeric enzyme, with each monomer consisting of an N-terminal α/β dinucleotide-binding domain and a C-terminal α-helical dimerization domain. The structure reveals key active-site residues at the domain interface, including His200, Arg297 and Ser179 that are involved in catalysis and/or ligand binding and are highly conserved in TyrA proteins from all three kingdoms of life. Tyrosine is bound directly at the catalytic site, suggesting that it is a competitive inhibitor of HinfPDH. Comparisons with its structural homologues reveal important differences around the active site, including the absence of an α-β motif in HinfPDH that is present in other TyrA proteins, such as Synechocystis sp. arogenate dehydrogenase. Residues from this motif are involved in discrimination between NADP(+) and NAD(+). The loop between β5 and β6 in the N-terminal domain is much shorter in HinfPDH and an extra helix is present at the C-terminus. Furthermore, HinfPDH adopts a more closed conformation compared with TyrA proteins that do not have tyrosine bound. This conformational change brings the substrate, cofactor and active-site residues into close proximity for catalysis. An ionic network consisting of Arg297 (a key residue for tyrosine binding), a water molecule, Asp206 (from the loop between β5 and β6) and Arg365' (from the additional C-terminal helix of the adjacent monomer) is observed that might be involved in gating the active site.

PubMed: 20944228
DOI: 10.1107/S1744309110021688

実験手法

X-RAY DIFFRACTION (2 Å)