Related ArticlesProbing the conformation of the sugar transport inhibitor phlorizin by 2D-NMR, molecular dynamics studies, and pharmacophore analysis.
J Med Chem. 2000 May 4;43(9):1692-8
Authors: Wielert-Badt S, Lin JT, Lorenz M, Fritz S, Kinne RK
Sodium/D-glucose cotransport, one of the prototypes for sodium gradient-driven symport systems in kidney and intestine, is known to be inhibited by aromatic and aliphatic glucosides (Diedrich, D. F. Biochim. Biophys. Acta 1963, 71, 688-700; Diedrich, D. F. Arch. Biochem. Biophys. 1966, 117, 248-256; Kipp, H.; et al. Biochim. Biophys. Acta 1996, 1282, 124-130; Ramaswamy, K.; et al. Biochim. Biophys. Acta 1976, 433, 32-38). The conformation in which the most potent inhibitor, phlorizin, interacts with the transport protein was investigated with different approaches. Phlorizin consists of the glucose moiety and two aromatic rings (A and B) joined by an alkyl spacer. First the interaction of these various parts of the molecule was determined by two-dimensional (2D) solution NMR. From the 2D-NOESY (nuclear Overhauser effect) measurements spatial distances (up to 5 A) between various interacting H atoms could be detected. Using these values as distance constraints, conformations of phlorizin were calculated and analyzed by the valence force-field method. As a result, a set of conformations could be obtained. The most probable phlorizin conformation shows a nearly perpendicular arrangement of the two aromatic rings (A and B) with the ring B situated above the sugar ring. A very similar conformation could be found by using molecular dynamics simulations when water was chosen as the solvent. This phlorizin conformation in aqueous solution then served as a template for conformational analysis of various phlorizin derivatives. The resulting conformations of derivatives were taken as input to establish a pharmacophore model using the DISCO calculation. As a result, the essential elements of phlorizin for interaction with its binding pocket could be deduced: namely hydrogen bonding via hydroxyl groups of the pyranoside at C(2), C(3), C(4), and C(6) and at C(4) and C(6) of aromatic ring A and hydrophobic interactions via the pyranoside ring and aromatic ring A. Finally, from these conformational features of the pharmacophore the dimension of the phlorizin binding site on the sodium/D-glucose cotransporter was estimated to be 17 x 10 x 7 A(3).
Probing the HIV gp120 envelope glycoprotein conformation by NMR.
Probing the HIV gp120 envelope glycoprotein conformation by NMR.
Probing the HIV gp120 envelope glycoprotein conformation by NMR.
J Biol Chem. 2011 Jul 8;286(27):23975-81
Authors: Celigoy J, Ramirez B, Tao L, Rong L, Yan L, Feng YR, Quinnan GV, Broder CC, Caffrey M
Abstract
The HIV envelope glycoprotein gp120 plays a critical role in virus entry, and thus, its structure is of extreme interest for the development of novel therapeutics and vaccines. To date, high resolution structural information about gp120 in complex with gp41 has proven...
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09-09-2011 06:42 PM
[NMR paper] Exploring the active site of human factor Xa protein by NMR screening of small molecu
Exploring the active site of human factor Xa protein by NMR screening of small molecule probes.
Related Articles Exploring the active site of human factor Xa protein by NMR screening of small molecule probes.
Org Biomol Chem. 2003 Dec 7;1(23):4235-41
Authors: Fielding L, Fletcher D, Rutherford S, Kaur J, Mestres J
A collection of small molecules (MW < 350 Da) was screened for binding to human factor Xa using saturation transfer difference NMR spectroscopy to detect binding. The NMR screening experiments identified four hits. Binding isotherms...
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11-24-2010 09:16 PM
Rapid, Accurate and Simple Model to Predict NMR Chemical Shifts for Biological Molecu
Rapid, Accurate and Simple Model to Predict NMR Chemical Shifts for Biological Molecules.
Rapid, Accurate and Simple Model to Predict NMR Chemical Shifts for Biological Molecules.
J Phys Chem B. 2010 Nov 18;
Authors: Atieh Z, Aubert-Fre?con M, Allouche AR
We present a new model to predict chemical shifts for biological molecules. It is simple, fast, and involves a limited number of parameters. It is particularly adapted to be used in molecular dynamics studies with a molecular mechanic potential. We test the model for polyamines, which are rather...
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11-20-2010 06:01 PM
[NMR paper] Selective NMR observation of inhibitor and sugar binding to the galactose-H(+) sympor
Selective NMR observation of inhibitor and sugar binding to the galactose-H(+) symport protein GalP, of Escherichia coli.
Related Articles Selective NMR observation of inhibitor and sugar binding to the galactose-H(+) symport protein GalP, of Escherichia coli.
Biochim Biophys Acta. 2000 Dec 20;1509(1-2):55-64
Authors: Appleyard AN, Herbert RB, Henderson PJ, Watts A, Spooner PJ
The binding of the transport inhibitor forskolin, synthetically labelled with (13)C, to the galactose-H(+) symport protein GalP, overexpressed in its native inner...
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11-19-2010 08:29 PM
[NMR paper] 31P-CP-MAS NMR studies on TPP+ bound to the ion-coupled multidrug transport protein E
31P-CP-MAS NMR studies on TPP+ bound to the ion-coupled multidrug transport protein EmrE.
Related Articles 31P-CP-MAS NMR studies on TPP+ bound to the ion-coupled multidrug transport protein EmrE.
FEBS Lett. 2000 Sep 1;480(2-3):127-31
Authors: Glaubitz C, Gröger A, Gottschalk K, Spooner P, Watts A, Schuldiner S, Kessler H
The binding of tetraphenylphosphonium (TPP+) to EmrE, a membrane-bound, 110 residue Escherichia coli multidrug transport protein, has been observed by 31P cross-polarisation-magic-angle spinning nuclear magnetic resonance...
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[NMR software blog] Oh, Sugar
Oh, Sugar
I have good news! With a minimal simplification of my INADEQUATE filter I have been able to rescue the last cross-peak of cholesterol. It had been rejected because too near to the diagonal. I changed the code saying: "if it's on the diagonal, it is bad; if it's just near, let's accept it". So it is possible to have the perfect INADEQUATE of cholesterol, with all the expected cross-peaks IN and everything else OUT.
Yesterday I received another INADEQUATE spectrum, this time of sucrose. The S/N is still high enough to make my filter unnecessary. If I play with the contour plot all...
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09-03-2010 04:16 PM
[NMR paper] Na(+)-H+ and Na(+)-Li+ exchange are mediated by the same membrane transport protein i
Na(+)-H+ and Na(+)-Li+ exchange are mediated by the same membrane transport protein in human red blood cells: an NMR investigation.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--pubs.acs.org-images-acspubs.jpg Related Articles Na(+)-H+ and Na(+)-Li+ exchange are mediated by the same membrane transport protein in human red blood cells: an NMR investigation.
Biochemistry. 1996 Sep 24;35(38):12433-42
Authors: Chi Y, Mo S, Mota de Freitas D
Na(+)-H+ exchange is a transport system present in erythrocytes which plays an important role in...
Probing the conformation of the sugar transport inhibitor phlorizin by 2D-NMR, molecu
Linear Mode
