Roopa Kothapalli

Uppsala University | UU · Department of Cell and Molecular Biology

L-aspartate α-decarboxylase (ADC) belongs to a class of pyruvoyl dependent enzymes and catalyzes the conversion of aspartate to β-alanine in the pantothenate pathway, which is critical for the growth of several micro-organisms, including Mycobacterium tuberculosis (Mtb). Its presence only in micro-organisms, fungi and plants and its absence in anim...

Binding poses of known inhibitors/ligands. The known inhibitors or ligands are shown as thick ball and stick. Atoms are colored as: H: white, C: green, N: blue, O: red and S: yellow. The interacting MtbADC residues are drawn as thin wireframe with the same color scheme and are labeled. Hydrogen bond interactions are shown as dotted yellow lines, al...

Pantothenate and CoA biosynthesis pathway. L-Aspartate α-decarboxylase (ADC) catalyzes the decarboxylation of L-aspartate to β-alanine. (TIFF)

The 28 ligand hits from the Maybridge, NCI and FDA databases which interact with at least one of the conserved functional residues of MtbADC residues involved in substrate binding and their glide score (kcal/mol). The ligands are ranked according to their glide scores in their respective databases. The ligands that interact with Pyr25 are in bold....

The structures of known and reported inhibitors against ADC. (TIFF)

Fumarate binding in ADC. (a) The superimposed view of the TthADC:fumarate crystal structure (red) and MtbADC:fumarate docking model (blue) is shown. The processed model for MtbADC was generated from the crystal structure of unprocessed protein and docking of fumarate was achieved using the Glide Extra Precision mode. The interacting conserved resid...

Ligands docked to monomeric MtbADC. The structures of the top three hits, obtained by docking the Maybridge, NCI and FDA databases with the processed monomeric MtbADC structure. These molecules are big and cannot be genuine inhibitors as the actual active site is formed in the cleft of a dimer with relatively smaller volume and only molecules of sm...

The ADMET properties of the 28 ligands. The ligands that interact with Pyr25 are in bold. The entries of Table 2 are underlined. The definitions of the properties are as in Table 2. (DOCX)

Interactions of selected known inhibitors/ligands with MtbADC as verified by Glide XP. (DOCX)

Glioblastoma multiforme (GBM) is considered to be the most common and often deadly disorder which affects the brain. It is caused by the over expression of proteins such as ephrin type-A receptor 2 (EphA2), epidermal growth factor receptor (EGFR) and EGFRvIII. These 3 proteins are considered to be the potential therapeutic targets for GBM. Among th...

The three-dimensional (3D) structure of the substrate binding domain (SBD) of human ubiquitin ligase Siah2 (seven in absentia homolog) was constructed based on the homology modeling approach using the Modeller 9v7 program. The molecular dynamics method was utilized to refine the model and it was further assessed by ProSA, three-dimensional structur...

Shigella dysenteriae continues to be a major health problem, which leads to death, due to diarrhoea and dysentery, predominantly in children below the age of 5. Bacterial invasion of the colonic epithelium leads to severe inflammation together with bacterial dissemination generates abscesses and ulcerations. Periplasmic copper, zinc super oxide dis...

ADMET properties calculated using Mobyle portal for the seven lead molecules. (0.04 MB DOC)

Number of sequences of the various MMPs studied. These sequences were obtained from the NCBI Entrez protein database by use of PSI-BLAST search (as of May 2009). (0.03 MB DOC)

NCBI Entrez protein database accession and GI numbers of the 50 sequences analysed in this study. (0.05 MB DOC)

The 25 screened ligands that interact with at least one residue of the HCR-13pf of MMP-13 (PDB ID: 1PEX) and their hydrogen bond interaction(s) to residues of MMP-1 (PDB ID: 1SU3) and -8 (PDB ID: 1BZS). 1SU3 structure contains both Hpx and catalytic domains, while 1BZS has only the catalytic domain. Rows shaded in grey are for the seven lead molecu...

Background: MMP-13, a zinc dependent protease which catalyses the cleavage of type II collagen, is expressed in osteoarthritis (OA) and rheumatoid arthritis (RA) patients, but not in normal adult tissues. Therefore, the protease has been intensively studied as a target for the inhibition of progression of OA and RA. Recent reports suggest that sel...