Lee Wen-Hwa, Perles Luis Augusto, Nagem Ronaldo A P, Shrive Annette K, Hawkins Alastair, Sawyer Lindsay, Polikarpov Igor
Laboratório Nacional de Luz Síncrotron/LNLS, Campinas, SP, Brazil.
Acta Crystallogr D Biol Crystallogr. 2002 May;58(Pt 5):798-804. doi: 10.1107/s0907444902003918. Epub 2002 Apr 26.
The type I 3-dehydroquinate dehydratase (DHQase) which catalyses the reversible dehydration of 3-dehydroquinic acid to 3-dehydroshikimic acid is involved in the shikimate pathway for the biosynthesis of aromatic compounds. The shikimate pathway is absent in mammals, which makes structural information about DHQase vital for the rational design of antimicrobial drugs and herbicides. The crystallographic structure of the type I DHQase from Salmonella typhi has now been determined for the native form at 1.78 A resolution (R = 19.9%; R(free) = 24.7%). The structure of the modified enzyme to which the product has been covalently bound has also been determined but in a different crystal form (2.1 A resolution; R = 17.7%; R(free) = 24.5%). An analysis of the three available crystal forms has provided information about the physiological dimer interface. The enzyme relies upon the closure of a lid-like loop to complete its active site. As the lid-loop tends to stay in the closed position, dimerization appears to play a role in biasing the arrangement of the loop towards its open position, thus facilitating substrate access.
I型3-脱氢奎尼酸脱水酶（DHQase）催化3-脱氢奎尼酸可逆脱水生成3-脱氢莽草酸，参与芳香族化合物生物合成的莽草酸途径。哺乳动物体内不存在莽草酸途径，这使得关于DHQase的结构信息对于合理设计抗菌药物和除草剂至关重要。伤寒沙门氏菌I型DHQase的晶体结构现已确定，天然形式的分辨率为1.78 Å（R = 19.9%；R（自由）= 24.7%）。与产物共价结合的修饰酶的结构也已确定，但为不同的晶体形式（分辨率2.1 Å；R = 17.7%；R（自由）= 24.5%）。对三种可用晶体形式的分析提供了有关生理二聚体界面的信息。该酶依靠一个类似盖子的环的闭合来形成其活性位点。由于盖子环倾向于保持在关闭位置，二聚化似乎在使环的排列偏向其打开位置方面发挥作用，从而便于底物进入。
