عنوان
پدید آورنده
موضوع
رده
کتابخانه
محل استقرار
شماره کتابشناسی ملی
شماره
TL52726
زبان اثر
زبان متن نوشتاري يا گفتاري و مانند آن
انگلیسی
عنوان و نام پديدآور
عنوان اصلي
Unravelling the Mechanism of Fdc1, a Novel prFMN Dependent Decarboxylase
نام عام مواد
[Thesis]
نام نخستين پديدآور
Bailey, Samuel S.
نام ساير پديدآوران
Leys, David
وضعیت نشر و پخش و غیره
نام ناشر، پخش کننده و غيره
The University of Manchester (United Kingdom)
تاریخ نشرو بخش و غیره
2018
يادداشت کلی
متن يادداشت
143 p.
یادداشتهای مربوط به پایان نامه ها
جزئيات پايان نامه و نوع درجه آن
Ph.D.
کسي که مدرک را اعطا کرده
The University of Manchester (United Kingdom)
امتياز متن
2018
یادداشتهای مربوط به خلاصه یا چکیده
متن يادداشت
The UbiD superfamily of enzymes are reversible decarboxylases that depend on the novel cofactor prenylated FMN (prFMN) for activity. The partner protein UbiX prenylates FMNH2 using dimethylallyl phosphate. The UbiX product, prFMNH2 is then passed to UbiD, where oxidative maturation to an active form, prFMNiminium occurs. Following oxidative activation, UbiD family members are able to catalyse the reversible decarboxylation of a wide range of unsaturated aliphatic and aromatic acids. The UbiD family contain a conserved active site E(D)RE motif that is proposed to play a role in cofactor maturation and decarboxylation. The Fdc1 enzyme from Aspergillus niger catalyses the decarboxylation of cinnamic acid and acts as a model system for studying UbiD enzymes, due to its amenability to high resolution crystallographic studies, ease of purification and readily detectable decarboxylation activity. Our studies on Fdc1 provide valuable insights into the role of the conserved ERE motif in cofactor maturation, isomerisation, and substrate (de)carboxylation. We confirm prFMNiminium is the active form, with illumination leading to inactivation through formation of the prFMNketimine isomer. We demonstrate ERE predominantly acts in catalysis, but not maturation or isomerisation. Our crystallographic studies of Fdc1 in complex with alkene substrates and alkyne inhibitors provides the first direct evidence for enzymatic 1,3-dipolar cycloaddition. These crystal structures also demonstrate a crucial role for molecular strain, whereby the enzyme is able to achieve reversible cycloaddition through selective destabilisation of key intermediates. Hence, we present strong evidence for the proposed 1,3-dipolar cycloaddition mechanism in case of enoic acid substrates. This leads to the question whether a similar mechanism also applies in case of aromatic acids, as occurs in distinct branches of the UbiD family. This remains a contentious issue, and will require future studies on distinct representatives of the UbiD-superfamily.
اصطلاحهای موضوعی کنترل نشده
اصطلاح موضوعی
Biochemistry
اصطلاح موضوعی
Organic chemistry
نام شخص به منزله سر شناسه - (مسئولیت معنوی درجه اول )
مستند نام اشخاص تاييد نشده
Bailey, Samuel S.
نام شخص - ( مسئولیت معنوی درجه دوم )
مستند نام اشخاص تاييد نشده
Leys, David
شناسه افزوده (تنالگان)
مستند نام تنالگان تاييد نشده
The University of Manchester (United Kingdom)
دسترسی و محل الکترونیکی
نام الکترونيکي
مطالعه متن کتاب وضعیت انتشار
فرمت انتشار
p
اطلاعات رکورد کتابشناسی
نوع ماده
[Thesis]
کد کاربرگه
276903
اطلاعات دسترسی رکورد
سطح دسترسي
a
تكميل شده
Y
