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101.
The sequencing of theMycobacterium tuberculosis (MTB) H37Rv genome has facilitated deeper insights into the biology of MTB, yet the functions of many MTB proteins are unknown.
We have used sensitive profile-based search procedures to assign functional and structural domains to infer functions of gene
products encoded in MTB. These domain assignments have been made using a compendium of sequence and structural domain families.
Functions are predicted for 78% of the encoded gene products. For 69% of these, functions can be inferred by domain assignments.
The functions for the rest are deduced from their homology to proteins of known function. Superfamily relationships between
families of unknown and known structures have increased structural information by ∼ 11%. Remote similarity detection methods
have enabled domain assignments for 1325 ‘hypothetical proteins’. The most populated families in MTB are involved in lipid
metabolism, entry and survival of the bacillus in host. Interestingly, for 353 proteins, which we refer to as MTB-specific,
no homologues have been identified. Numerous, previously unannotated, hypothetical proteins have been assigned domains and
some of these could perhaps be the possible chemotherapeutic targets. MTB-specific proteins might include factors responsible
for virulence. Importantly, these assignments could be valuable for experimental endeavors. The detailed results are publicly
available at http://hodgkin.mbu.iisc.ernet.in/∼dots.
An erratum to this article is available at . 相似文献
102.
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104.
Conservation of structural fluctuations in homologous protein kinases and its implications on functional sites
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Our aim is to explore the similarities in structural fluctuations of homologous kinases. Gaussian Network Model based Normal Mode Analysis was performed on 73 active conformation structures in Ser/Thr/Tyr kinase superfamily. Categories of kinases with progressive evolutionary divergence, viz. (i) Same kinase with many crystal structures, (ii) Within‐Subfamily, (iii) Within‐Family, (iv) Within‐Group, and (v) Across‐Group, were analyzed. We identified a flexibility signature conserved in all kinases involving residues in and around the catalytic loop with consistent low‐magnitude fluctuations. However, the overall structural fluctuation profiles are conserved better in closely related kinases (Within‐Subfamily and Within‐family) than in distant ones (Within‐Group and Across‐Group). A substantial 65.4% of variation in flexibility was not accounted by variation in sequences or structures. Interestingly, we identified substructural residue‐wise fluctuation patterns characteristic of kinases of different categories. Specifically, we recognized statistically significant fluctuations unique to families of protein kinase A, cyclin‐dependent kinases, and nonreceptor tyrosine kinases. These fluctuation signatures localized to sites known to participate in protein‐protein interactions typical of these kinase families. We report for the first time that residues characterized by fluctuations unique to the group/family are involved in interactions specific to the group/family. As highlighted for Src family, local regions with differential fluctuations are proposed as attractive targets for drug design. Overall, our study underscores the importance of consideration of fluctuations, over and above sequence and structural features, in understanding the roles of sites characteristic of kinases. Proteins 2016; 84:957–978. © 2016 Wiley Periodicals, Inc. 相似文献
105.
The overall function of a multi‐domain protein is determined by the functional and structural interplay of its constituent domains. Traditional sequence alignment‐based methods commonly utilize domain‐level information and provide classification only at the level of domains. Such methods are not capable of taking into account the contributions of other domains in the proteins, and domain‐linker regions and classify multi‐domain proteins. An alignment‐free protein sequence comparison tool, CLAP (CLAssification of Proteins) was previously developed in our laboratory to especially handle multi‐domain protein sequences without a requirement of defining domain boundaries and sequential order of domains. Through this method we aim to achieve a biologically meaningful classification scheme for multi‐domain protein sequences. In this article, CLAP‐based classification has been explored on 5 datasets of multi‐domain proteins and we present detailed analysis for proteins containing (1) Tyrosine phosphatase and (2) SH3 domain. At the domain‐level CLAP‐based classification scheme resulted in a clustering similar to that obtained from an alignment‐based method. CLAP‐based clusters obtained for full‐length datasets were shown to comprise of proteins with similar functions and domain architectures. Our study demonstrates that multi‐domain proteins could be classified effectively by considering full‐length sequences without a requirement of identification of domains in the sequence. 相似文献
106.
Yiran Liu David Castano Francesco Girolamo Laia Trigueros-Motos Han-Gyu Bae Suat Peng Neo Jeongah Oh Pradeep Narayanaswamy Federico Torta Kerry Anne Rye Dong-Gyu Jo Jayantha Gunaratne Sangyong Jung Daniela Virgintino Roshni R. Singaraja 《Journal of lipid research》2022,63(1):100147
The myelin sheath, which is wrapped around axons, is a lipid-enriched structure produced by mature oligodendrocytes. Disruption of the myelin sheath is observed in several neurological diseases, such as multiple sclerosis. A crucial component of myelin is sphingomyelin, levels of which can be increased by ABCA8, a member of the ATP-binding cassette transporter family. ABCA8 is highly expressed in the cerebellum, specifically in oligodendroglia. However, whether ABCA8 plays a role in myelination and mechanisms that would underlie this role remain unknown. Here, we found that the absence of Abca8b, a mouse ortholog of ABCA8, led to decreased numbers of cerebellar oligodendrocyte precursor cells (OPCs) and mature oligodendrocytes in mice. We show that in oligodendrocytes, ABCA8 interacts with chondroitin sulfate proteoglycan 4 (CSPG4), a molecule essential for OPC proliferation, migration, and myelination. In the absence of Abca8b, localization of CSPG4 to the plasma membrane was decreased, contributing to reduced cerebellar CSPG4 expression. Cerebellar CSPG4+ OPCs were also diminished, leading to decreased mature myelinating oligodendrocyte numbers and cerebellar myelination levels in Abca8b?/? mice. In addition, electron microscopy analyses showed that the number of nonmyelinated cerebellar axons was increased, whereas cerebellar myelin thickness (g-ratio), myelin sheath periodicity, and axonal diameter were all decreased, indicative of disordered myelin ultrastructure. In line with disrupted cerebellar myelination, Abca8b?/? mice showed lower cerebellar conduction velocity and disturbed locomotion. In summary, ABCA8 modulates cerebellar myelination, in part through functional regulation of the ABCA8-interacting protein CSPG4. Our findings suggest that ABCA8 disruption may contribute to the pathophysiology of myelin disorders. 相似文献
107.
Ummul Haninah A Vasan SS Ravindran T Chandru A Lee HL Shamala Devi S 《Tropical biomedicine》2010,27(3):611-623
This paper reports the development of a one-step SYBR-Green I-based realtime RT-PCR assay for the detection and quantification of Chikungunya virus (CHIKV) in human, monkey and mosquito samples by targeting the E1 structural gene. A preliminary evaluation of this assay has been successfully completed using 71 samples, consisting of a panel of negative control sera, sera from healthy individuals, sera from patients with acute disease from which CHIKV had been isolated, as well as monkey sera and adult mosquito samples obtained during the chikungunya fever outbreak in Malaysia in 2008. The assay was found to be 100-fold more sensitive than the conventional RT-PCR with a detection limit of 4.12x10(0) RNA copies/μl. The specificity of the assay was tested against other related viruses such as Dengue (serotypes 1-4), Japanese encephalitis, Herpes Simplex, Parainfluenza, Sindbis, Ross River, Yellow fever and West Nile viruses. The sensitivity, specificity and efficiency of this assay were 100%, 100% and 96.8% respectively. This study on early diagnostics is of importance to all endemic countries, especially Malaysia, which has been facing increasingly frequent and bigger outbreaks due to this virus since 1999. 相似文献
108.
Cyclic and linear oligosaccharides constituted with 2-deoxy sugar units are synthesized by an oligomerization reaction involving activated thioglycoside monomers, consisting of a 2-deoxy sugar unit. The oligomerization promoter plays an important role in the formation of either the cyclic- or the linear oligosaccharides. Encapsulation abilities of a 2-deoxy cyclic hexamer with p-nitrophenol, by a 1H NMR method, showed complexation of the guest molecule with the host molecule. 相似文献
109.
Crystal structures of eight peptide β-hairpins in the sequence Boc-Leu-Phe-Val-Xxx-Yyy-Leu-Phe-Val-OMe revealed that the Phe(2) and Phe(7) aromatic rings are in close spacial proximity, with the centroid-centroid distance (R(cen)) of 4.4-5.4 ? between the two phenyl rings. Proton NMR spectra in chloroform and methanol solution reveal a significant upfield shift of the Phe(7) C(δ,δ') H(2) protons (6.65-7.04 ppm). Specific assignments of the aromatic protons have been carried out in the peptide Boc-Leu-Phe-Val-(D)Pro-(L)Pro-Leu-Phe-Val-OMe (6). The anticipated ring current shifts have been estimated from the aromatic ring geometrics observed in crystals for all eight peptides. Only one of the C(δ,δ') H proton lies in the shielding zone with rapid ring flipping, resulting in averaging between the two extreme chemical shifts. An approximate estimate of the population of conformations, which resemble crystal state orientation, may be obtained. Key nuclear Overhauser effects (NOEs) between facing Phe side chains provide support for close similarity between the solid state and solution conformation. Temperature dependence of aromatic ring proton chemical shift and line widths for peptide 6 (Boc-Leu-Phe-Val-(D)Pro-(L)Pro-Leu-Phe-Val-OMe) and the control peptide Boc-Leu-Val-Val-(D)Pro-Gly-Leu-Phe-Val-OMe establish an enhanced barrier to ring flipping when the two Phe rings are in proximity. Modeling studies suggest that small, conformational adjustment about C(α)-C(β) (χ(1) ) and C(β)-C(γ) (χ(2) ) bonds of both the Phe residues may be required in order to permit unhindered, uncorrelated flipping of both the Phe rings. The maintenance of the specific aromatic ring orientation in organic solvents provides evidence for significant stabilizing interaction. 相似文献
110.
Venkata Pulla Rao Vendra Garima Agarwal Sushil Chandani Venu Talla Narayanaswamy Srinivasan Dorairajan Balasubramanian 《PloS one》2013,8(8)