Refine Search

New Search

Results: 8

(searched for: doi:10.1080/07391102.2012.712458)
Save to Scifeed
Page of 1
Articles per Page
by
Show export options
  Select all
Saima Reyaz, Alvea Tasneem, Gyan Prakash Rai,
Journal of Molecular Graphics and Modelling, Volume 109; https://doi.org/10.1016/j.jmgm.2021.108021

The publisher has not yet granted permission to display this abstract.
Hemant Kumar, Suraj Kumar Mandal, Prerana Gogoi,
Journal of Biomolecular Structure and Dynamics pp 1-12; https://doi.org/10.1080/07391102.2021.1938683

Abstract:
Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases known to degrade extracellular matrix (ECM). Being involved in many biological and physiological processes of tissue remodeling, MMPs play a crucial role in many pathological conditions such as arthritis, cancer, cardiovascular diseases, etc. Typically, MMPs possess a propeptide, a zinc-containing catalytic domain, a hinge region and a hemopexin domain. Based on their structural domain organization and substrates, MMPs are classified into six different classes, viz. collagenases, stromelysins, gelatinases, matrilysins, membrane-type and other MMPs. As per previous studies, a set of invariant water (IW) molecules of MMP-1 (a collagenase) play a significant role in stabilizing their catalytic domain. However, a functional role of IW molecule in other classes of MMPs has not been reported yet. Thus, in this study, IW molecules of MMPs from different classes were located and their plausible role(s) have been assigned. The results suggest that IW molecules anchor the structurally and functionally essential metal ions present in the vicinity of the active site of MMPs. Further, they (in)directly interlink different structural features and bridge the active site metal ions of MMPs. This study provides the key IW molecules that are structurally and functionally relevant to MMPs and hence, in turn, might facilitate the development of potent generalized inhibitor(s) against different classes of MMPs. Communicated by Ramaswamy H. Sarma
Published: 30 March 2020
Bioinformation, Volume 16, pp 209-218; https://doi.org/10.6026/97320630016209

Abstract:
The human ceruloplasmin (hCP) is the copper containing ferroxidase enzyme with multifunctional activities (NO-oxidase, NO2-synthase,oxidation of neurotransmitters including antioxidants). Therefore, it is of interest to probe the multi-domain hCP using moleculardynamics simulation. Results explain the role played by several conserved water centers in the intra and inter-domain recognition throughH-bond interaction with the interacting residues. We observed seventeen conserved water centers in the inter-domain recognition. Weshow that five invariant water centers W13, W14, W18, W23 and W26 connect the Domain 5 to Domain 4 (D5…W…W4). We also show thatfive other water centers W19, W20, W27, W30 and W31 connects the Domain 5 to Domain 6 (D5…W…W6) that is unique in the simulatedform. The W7 and W32 water centers are involved in the D1…W…W6 recognition. This is important for the water-mediated interaction ofGlu1032 to the trinuclear copper cluster present at the interface between these domains. The involvement of W10 water center in theD3…W10…D4 recognition through Gln552…W10…His667 H-bond interaction is critical in the complexation of CP with myeloperoxidase(Mpo). These observations provide insights to the molecular recognition of hCP with other biomolecules in the system.
Published: 20 January 2017
Biochemistry (Moscow), Volume 82, pp 46-59; https://doi.org/10.1134/s0006297917010059

Abstract:
The plasma membrane Pma1 H+-ATPase of the yeast Saccharomyces cerevisiae contains conserved residue Asp739 located at the interface of transmembrane segment M6 and the cytosol. Its replacement by Asn or Val (Petrov et al. (2000) J. Biol. Chem., 275, 15709-15716) or by Ala (Miranda et al. (2011) Biochim. Biophys. Acta, 1808, 1781-1789) caused complete blockage of biogenesis of the enzyme, which did not reach secretory vesicles. It was proposed that a strong ionic bond (salt bridge) could be formed between this residue and positively charged residue(s) in close proximity, and the replacement D739A disrupted this bond. Based on a 3D homology model of the enzyme, it was suggested that the conserved Arg811 located in close proximity to Asp739 could be such stabilizing residue. To test this suggestion, single mutants with substituted Asp739 (D739V, D739N, D739A, and D739R) and Arg811 (R811L, R811M, R811A, and R811D) as well as double mutants carrying charge-neutralizing (D739A/R811A) or charge-swapping (D739R/R811D) substitutions were used. Expression of ATPases with single substitutions R811A and R811D were 38-63%, and their activities were 29-30% of the wild type level; ATP hydrolysis and H+ transport in these enzymes were essentially uncoupled. For the other substitutions including the double mutations, the biogenesis of the enzyme was practically blocked. These data confirm the important role of Asp739 and Arg811 residues for the biogenesis and function of the enzyme, suggesting their importance for defining H+ transport determinants but ruling out, however, the existence of a strong ionic bond (salt bridge) between these two residues and/or importance of such bridge for structure–function relationships in Pma1 H+-ATPase.
Jun Zou, Zhaodong Han, Liang Zhou, Chao Cai, Hongwei Luo, Yaqiang Huang, Yuxiang Liang, Huichan He, Funeng Jiang, , et al.
Published: 3 December 2014
Medical Oncology, Volume 32; https://doi.org/10.1007/s12032-014-0373-1

The publisher has not yet granted permission to display this abstract.
, Deepak K. Mishra, , K. Sekar
Journal of Biomolecular Structure and Dynamics, Volume 32, pp 1248-1262; https://doi.org/10.1080/07391102.2013.812982

Abstract:
Inosine monophosphate dehydrogenase (IMPDH) enzyme involves in GMP biosynthesis pathway. Type I hIMPDH is expressed at lower levels in all cells, whereas type II is especially observed in acute myelogenous leukemia, chronic myelogenous leukemia cancer cells, and 10 ns simulation of the IMP–NAD+ complex structures (PDB ID. 1B3O and 1JCN) have revealed the presence of a few conserved hydrophilic centers near carboxamide group of NAD+. Three conserved water molecules (W1, W, and W1′) in di-nucleotide binding pocket of enzyme have played a significant role in the recognition of carboxamide group (of NAD+) to D274 and H93 residues. Based on H-bonding interaction of conserved hydrophilic (water molecular) centers within IMP–NAD+-enzyme complexes and their recognition to NAD+, some covalent modification at carboxamide group of di-nucleotide (NAD+) has been made by substituting the –CONH2group by –CONHNH2 (carboxyl hydrazide group) using water mimic inhibitor design protocol. The modeled structure of modified ligand may, though, be useful for the development of antileukemic agent or it could be act as better inhibitor for hIMPDH-II.
Page of 1
Articles per Page
by
Show export options
  Select all
Back to Top Top