Structural studies of tri-functional human GART

نویسندگان

  • Martin Welin
  • Jörg Günter Grossmann
  • Susanne Flodin
  • Tomas Nyman
  • Pål Stenmark
  • Lionel Trésaugues
  • Tetyana Kotenyova
  • Ida Johansson
  • Pär Nordlund
  • Lari Lehtiö
چکیده

Human purine de novo synthesis pathway contains several multi-functional enzymes, one of which, tri-functional GART, contains three enzymatic activities in a single polypeptide chain. We have solved structures of two domains bearing separate catalytic functions: glycinamide ribonucleotide synthetase and aminoimidazole ribonucleotide synthetase. Structures are compared with those of homologous enzymes from prokaryotes and analyzed in terms of the catalytic mechanism. We also report small angle X-ray scattering models for the full-length protein. These models are consistent with the enzyme forming a dimer through the middle domain. The protein has an approximate seesaw geometry where terminal enzyme units display high mobility owing to flexible linker segments. This resilient seesaw shape may facilitate internal substrate/product transfer or forwarding to other enzymes in the pathway.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Intronic polyadenylation in the human glycinamide ribonucleotide formyltransferase gene.

The mouse glycinamide ribonucleotide formyltransferase (GART) locus is known to produce two functional proteins, one by recognition and use of an intronic polyadenylation site and the other by downstream splicing. We now report a similar intronic polyadenylation mechanism for the human GART locus. The human GART gene has two potential polyadenylation signals within the identically located intro...

متن کامل

A tri state mechanism for oxygen release in fish hemoglobin: Using Barbus sharpeyi as a model

Hemoglobin is a porphyrin containing protein with an a2b2 tetrameric structure and like other porphyrin compounds shows spectral behavior of species specific characteristics. Researchers tend to relate bands in the hemoglobin spectra to certain structural and/or functional features. Given the fact that hemoglobin is the main oxygen carrier in animals functioning through the Oxy«Deoxy equilibriu...

متن کامل

Using a residue clash map to functionally characterize protein recombination hybrids.

In this article, we introduce a rapid, protein sequence database-driven approach to characterize all contacting residue pairs present in protein hybrids for inconsistency with protein family structural features. This approach is based on examining contacting residue pairs with different parental origins for different types of potentially unfavorable interactions (i.e. electrostatic repulsion, s...

متن کامل

DFT studies of all fluorothiophenes and their radical cations as candidate monomers for conductive polymers

In this paper, electronic, structural, and spectroscopic properties of mono-, di-, tri-, andtetrafluorothiophenes and their radical cations are studied using the density functional theory andB3LYP method with 6-311++G** basis set. Also the effects of the number and position of thesubstituent on the electrochemical properties of the thiophene ring have been studied usingoptimized structures obta...

متن کامل

Glucose and Fluoxetine Induce Fine Structural Change in Human Serum Albumin

Human serum albumin has been used as a model protein for protein folding and ligand binding studies over many decades. Due to its long life period and high concentration in plasma, HSA is highly sensitive to glycation. It is reported that 175 mg/dL glucose concentration is a threshold of kidney activity for the beginning of excretion of glucose. pH denaturation of HSA in absence and presence of...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 38  شماره 

صفحات  -

تاریخ انتشار 2010