Mohamad Aman Jairajpuri's research while affiliated with Jamia Millia Islamia and other places

Publications (66)

Article
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Neuroserpin (NS) is predominantly expressed in the brain and is the primary inhibitor of tissue plasminogen activator (tPA). NS variants are associated with the neurogenerative disease termed, familial encephalopathy with neuroserpin inclusion bodies (FENIB), the disease is characterized by variable age of onset and severity. The reactive center lo...
Article
α-1-antichymotrypsin (ACT) is a serine proteinase inhibitor that controls the activity of proteases like chymotrypsin, cathepsin G and mast cell chymase. Familial variants of ACT results in liver and lung diseases, but it is also reported to be associated with several other disease conditions. ACT is mainly synthesized in the liver using four codin...
Article
Thromboembolic diseases are a major cause of mortality in human and the currently available anticoagulants are associated with various drawbacks, therefore the search for anticoagulants that have better safety profile is highly desirable. Compounds that are part of the dietary routine can be modified to possibly increase their anticoagulant potenti...
Article
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Neuroserpin is a serine protease inhibitor expressed mainly in the brain and at low levels in other tissues like the kidney, testis, heart, and spinal cord. It is involved in the inhibition of tissue plasminogen activator (tPA), plasmin, and to a lesser extent, urokinase‐type plasminogen (uPA). Neuroserpin has also been shown to plays non‐inhibitor...
Article
Neuroserpin (NS) is an inhibitory protein of serpin super family, its shutter region variants have high propensity to aggregate leading to pathological disorders like familial encephalopathy with NS inclusion bodies (FENIB). Helix F and β-sheet A of NS participate in the tissue plasminogen activator (tPA) inhibition but the mechanism is not yet com...
Article
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Antithrombin (AT) deficiency is a rare but strong risk factor for the thrombosis development. Mutations in gene encoding AT (SERPINC1) have provided a detailed understanding of AT deficiency and subsequent development of thrombotic complications. In the present study, we describe a case of thrombotic patient with reduced AT activity and normal AT a...
Article
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Human serine protease inhibitors (serpins) are the main inhibitors of serine proteases, but some of them also have the capability to effectively inhibit cysteine proteases. Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) main protease (Mpro) is a chymotrypsin-type cysteine protease that is needed to produce functional proteins essentia...
Article
Heparin cofactor II (HCII) is predominantly expressed in the liver and inhibits thrombin in blood plasma to influence the blood coagulation cascade. Its deficiency is associated with arterial thrombosis. Its cleavage by neutrophil elastase produces fragment that helps in neutrophil chemotaxis in the acute inflammatory response in human. In the pres...
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Aims Design and synthesis of a novel 3, 3', 4', 5, 7-O- pentasulfated Quercetin (QPS) as activator of protein disulfide isomerase (PDI). Main Methods Based on an in silico analysis we show that QPS binds to a and b domain of PDI (-7.4 kcal/mol) unlike PDI inhibitor quercetin 3-rutinoside (Q3R) that binds at substrate binding domain b (-8.0 kcal/mo...
Article
Increased tendency of cancer patient to develop venous thromboembolism (VTE) is associated with high rates of mortality. Elevation of procoagulant proteins and down regulation of naturally occurring coagulation inhibitors appears to form the basis of high risk of VTE in malignancy. A reduced level of anticoagulant protein like antithrombin (AT) wil...
Article
Neuroserpin (NS) is predominantly expressed in brain and inhibits tissue-type plasminogen activator (tPA) with implications in brain development and memory. Nature of conformational change in pathological variants in strand 6B and helix B of NS that cause a relatively mild to severe epilepsy (and/or dementia) remains largely elusive. MD simulation...
Article
Due to the potential toxicity of mercury, there is an immediate need to understand its uptake, transport and flux within living cells. Conventional techniques used to analyze Hg²⁺ are invasive, involve high cost and are less sensitive. In the present study, a highly efficient genetically encoded mercury FRET sensor (MerFS) was developed to measure...
Article
Antithrombin (AT3) is one of the most important inhibitors of blood coagulation proteases that belong to the serpin family of protease inhibitors. In this study, a novel alternatively spliced isoform of AT3 was identified, both at transcript and protein level. This novel transcript contains an additional region in the continuation of exon 3b that w...
Article
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Serine protease inhibitors (serpins) family have a complex mechanism of inhibition that requires a large scale conformational change. Antithrombin (AT), a member of serpin superfamily serves as a key regulator of the blood coagulation cascade, deficiency of which leads to thrombosis. In recent years, a handful of studies have identified small compo...
Article
Currently available anticoagulants for prevention and treatment of thrombosis have several limitations, thus, small organic scaffolds that can dissolve clots in vivo in a dose dependent manner with lesser side effects are highly desirable. Here we report the synthesis of esculin pentasulfate (EPS) and assessment of its in vitro, in vivo and ex vivo...
Article
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No efficient treatment exists for nephrotic syndrome (NS), a frequent cause of chronic kidney disease. Here we show mutations in six different genes (MAGI2, TNS2, DLC1, CDK20, ITSN1, ITSN2) as causing NS in 17 families with partially treatment-sensitive NS (pTSNS). These proteins interact and we delineate their roles in Rho-like small GTPase (RLSG)...
Article
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Steroid-resistant nephrotic syndrome (SRNS) is a frequent cause of chronic kidney disease. Here, we identified recessive mutations in the gene encoding the actin-binding protein advillin (AVIL) in 3 unrelated families with SRNS. While all AVIL mutations resulted in a marked loss of its actin-bundling ability, truncation of AVIL also disrupted coloc...
Article
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Neuroserpin (NS) mediated inhibition of tissue-type plasminogen activator (tPA) is important for brain development, synapse formation and memory. Aberrations in helix F and β-sheet A movement during inhibition can directly lead to epilepsy or dementia. Conserved W154 residue in a hydrophobic patch between helix F and β-sheet A is ideally placed to...
Article
The increasing incidence of human candidiasis and its tendency to become resistant to existing chemotherapies is a well-recognized health problem. The present study demonstrates the successful synthesis of novel triazole-amino acid hybrids with potent in vitro and in vivo inhibitory activity against Candida species. Particularly, compounds 68 and 7...
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The sorghum (Sorghum bicolor) genome contains a number of putative serpins (serine protease inhibitor) that are expressed under varying conditions, but little is known about their biological function. One of the sorghum serpin genes encodes a protein that contains reactive center residues Leu-Arg-X (X = small residue), called a LR serpin. Similar p...
Article
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Antithrombin III (AT) is the most important endogenous anticoagulant, and genetic variability in SERPINC1, gene encoding AT, is low. Mutations leading to AT deficiency and increased thrombotic risk are well known; however, only 2 studies have reported mutations in regulatory region of SERPINC1 gene till date. Aim of the present study was to identif...
Article
Pro-coagulant, anti-coagulant and fibrinolytic pathways are responsible for maintaining haemostatic balance under physiological conditions. Any deviation from these pathways would result in hypercoagulability leading to life threatening diseases like myocardial infarction, stroke, portal vein thrombosis, deep vein thrombosis (DVT) and pulmonary emb...
Article
Rapidly increasing resistance to the currently available antimalarial drugs has drawn attention globally for the search of more potent novel drugs with high therapeutic index. The genome sequencing of human malarial parasite Plasmodium falciparum has provided extensive information to understand potential target pathways and efforts are being made t...
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Phenotypic resistance to activated protein C (APC) is a complex mechanism associated with increased thrombosis risk. Activated protein C resistance (APCR) is mainly influenced by FVLeiden mutation, and various other single nucleotide polymorphisms (SNPs) in FV gene are known to be associated with APCR. The aim of present study was to investigate th...
Article
Endogenous proteins that promote vascular endothelial cell based inhibition of angiogenesis are an attractive option for antitumor therapy. Inactive cleaved and latent conformations of antithrombin (AT) are antiangiogenic, but not its native form which is an inhibitor of proteases involved in blood coagulation. Unlike native, the cleaved and latent...
Article
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Antithrombin III (AT) is the main inhibitor of blood coagulation proteases like thrombin and factor Xa. In this study we report the identification and characterization of several variants of AT for the first time in Indian population. We screened 1950 deep vein thrombosis (DVT) patients for AT activity and antigen levels. DNA sequencing was further...
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Physiological hemostatic balance is a coordinated outcome of counteracting coagulation and fibrinolytic systems. An imbalance of procoagulant and anticoagulant factors may result in life threatening thromboembolism. Presently, anticoagulant administration is the first line of therapy for the treatment of these conditions and several anticoagulants...
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Recurrent pregnancy loss (RPL) can be caused due to diverse factors with thrombophilia being one of them. The association of various thrombophilic risk factors with RPL is inconsistent in different studies and the frequency of these risk factors in Indian population is obscure. Five hundred and eighty patients with either recurrent early miscarriag...
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The importance of domain II in the molecular interaction of bovine serum albumin (BSA) with curcumin was investigated by fluorescence spectroscopy and molecular docking. At pH 7.4 BSA is in its native state. Domain III of BSA unfolds at pH 4.0, and domains I and III unfold in the presence of 5 M urea. Curcumin has a high quenching constant (K SV ~...
Article
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Serpins such as antithrombin, heparin cofactor II, plasminogen activator inhibitor, antitrypsin, antichymotrypsin, and neuroserpin are involved in important biological processes by inhibiting specific serine proteases. Initially, the protease recognizes the mobile reactive loop of the serpin eliciting conformational changes, where the cleaved loop...
Article
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Antithrombin, the principal inhibitor of coagulation proteases, requires allosteric activation by its physiological cofactor, heparin or heparin sulfate to achieve physiologically permissible rates. This forms the basis of heparin's use as a clinical anticoagulant. However, heparin therapy is beset with severe complications, giving rise to the need...
Article
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With "reactive" arginine as a kinetic reporter, 2-hydroxyacid dehydrogenases are assessed in basis of their specialization as NAD(+)-reducing or NADH-oxidizing enzymes. Specifically, M4 and H4 lactate dehydrogenases (LDHs) and cytoplasmic and mitochondrial malate dehydrogenases (MDHs) are compared to assess if their coenzyme specificity may involve...
Article
Serine Protease inhibitors (serpins) are a super-family of proteins that controls the proteinases involved in the inflammation, complementation, coagulation and fibrinolytic pathways. Serpins are prone to conformational diseases due a complex inhibition mechanism that involves large scale conformational change, their susceptibility to undergo point...
Article
Protein insertion sequences and their biological role in many organisms have been largely unknown. Here we study proteomes of 12 organisms originating from diverse genomes for insertion length and amino acid preferences. A total of 871 common proteins were catalogued amongst the 12 organisms for structure based sequence alignment. This underscores...
Article
Background: Over the last few decades, metal-based drugs, particularly cisplatin and its analogs have been used for the treatment of various cancers. Currently, scientists are developing other metal complexes as anticancer agents to eliminate the toxicity associated with platinum drugs. Results: Claisen-Schmidt condensation was used to synthesiz...
Article
Summary Future Medicinal Chemistry February 2013, Vol. 5, No. 2, Pages 135-146 Research Article Synthesis, DNA binding, hemolysis assays and anticancer studies of copper(II), nickel(II) and iron(III) complexes of a pyrazoline-based ligand Kishwar Saleem*1, Waseem A Wani1, Ashanul Haque1, Mohamad Nadeem Lone1, Ming-Fa Hsieh2, Mohamad Aman Jairajpu...
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Endogenous angiogenesis inhibitor that specifically decreases tumor cell proliferation can be used to treat cancer since angiogenesis is required at every step of tumor progression and metastasis. Endothelial cells are the main target for the antiangiogenic therapy because they are non-transformed and easily accessible to angiogenic inhibitors. Ant...
Article
Antithrombin III (ATIII) is the main inhibitor of the coagulation proteases like factor Xa and thrombin. Anticoagulant activity of ATIII is increased by several thousand folds when activated by vascular wall heparan sulfate proteoglycans (HSPGs) and pharmaceutical heparins. ATIII isoforms in human plasma, alpha-ATIII and beta-ATIII differ in the am...
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Molecular chaperones are a class of proteins responsible for proper folding of a large number of polypeptides in both prokaryotic and eukaryotic cells. Newly synthesized polypeptides are prone to nonspecific interactions, and many of them make toxic aggregates in absence of chaperones. The eukaryotic chaperonin CCT is a large, multisubunit, cylindr...
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Serpin constitute about 10% of blood protein and are associated with mutations that results in aberrant intermolecular linkages which leads to polymer formation. Studies with short peptides have shown promise in depolymerization of serpins however a reactive center loop based peptide also makes the serpin inactive. A chemical chaperone based approa...
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The serpins (serine proteinase inhibitors) are structurally similar but functionally diverse proteins that fold into a conserved structure and employ a unique suicide substrate-like inhibitory mechanism. Serpins play absolutely critical role in the control of proteases involved in the inflammatory, complement, coagulation and fibrinolytic pathways...
Article
Unlabelled: Serine Protease inhibitors (Serpins) like antithrombin, antitrypsin, neuroserpin, antichymotrypsin, protein C-inhibitor and plasminogen activator inhibitor is involved in important biological functions like blood coagulation, fibrinolysis, inflammation, cell migration and complement activation. Serpins native state is metastable, which...
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Plasmodium parasites are causative agents of malaria which affects >500 million people and claims approximately 2 million lives annually. The completion of Plasmodium genome sequencing and availability of PlasmoDB database has provided a platform for systematic study of parasite genome. Aminoacyl-tRNA synthetases (aaRSs) are pivotal enzymes for pro...
Data
Phylogenetic trees of aaRSs from P. falciparum. The evolutionary tree was constructed by the method PHYML using the MEGA 4.0. P. falciparum aaRSs are labeled green triangles. 102 species considered for the evolutionary analysis are taken from the three domains of life viz. P. berghei, P. chabaudi, P. falciparum, P. knowlesi, P. yoelii, P. vivax, H....
Data
List of Pf-aaRSs categorized into class I, class II, and related proteins. Gene ID, gene location, description of product and its length are given.
Article
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The native conformation of antithrombin III (ATIII) is a poor inhibitor of its coagulation pathway target enzymes because of the partial insertion of its reactive center loop (RCL) in its central A beta-sheet. This study focused on tyrosine 131, which is located at the helix D-sheet A interface, adjacent to the ATIII pentasaccharide and heparin cof...
Article
Full-text available
The native conformation of antithrombin III (ATIII) is a poor inhibitor of its coagulation pathway target enzymes because of the partial insertion of its reactive center loop (RCL) in its central A β-sheet. This study focused on tyrosine 131, which is located at the helix D-sheet A interface, adjacent to the ATIII pentasaccharide and heparin cofact...
Article
Full-text available
The dissociation equilibrium constant for heparin binding to antithrombin III (ATIII) is a measure of the cofactor's binding to and activation of the proteinase inhibitor, and its salt dependence indicates that ionic and non-ionic interactions contribute approximately 40 and approximately 60% of the binding free energy, respectively. We now report...
Article
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The mechanism for heparin activation of antithrombin III has been postulated to involve disruption of interactions between its reactive loop P1 residue and Glu(255) on the underlying protein surface. To test this hypothesis, the potential P1-constraining Arg(393)-Glu(255) hydrogen bond and ionic interactions were eliminated by converting Glu(255) t...
Article
Following a long-standing suggestion of Riordan et al. [Riordan, J. F., McElvany, K. D., and Borders, C. L., Jr. (1977) Science 195, 884-885], we sought to exploit chemically activated arginines as probes to characterize the microenvironmental effects in enzymes that mediate the recognition of anionic substrates. A micellar simulation study establi...

Citations

... In one of the possibilities, exon E1 is replaced by exon N1, which leads to the formation of a protein with an altered N-terminal sequence. In turn, changing the splicing site at the end of exon E3 introduces an additional 12 nt containing the stop codon, which leads to the formation of a protein without the RCL sequence encoded by exon E4 ( Figure 1C) [7]. The form called ACT-N appears to be catalytically active but may show reduced substrate binding capacity. ...
... 36 In addition, SERPINA3 levels seems to be increased in the disease. 35 Interestingly, recombinant SERPINs with cysteine protease activity have been suggested as a trap to SARS-CoV-2 M pro , since the viral enzyme is a cysteine protease, 148 but the success of this idea still needs to be investigated. It has been shown that SERPINA1 is able to inhibit TMPRSS2 in a 18 | FÉ ET AL. ...
... The novel exons were predicted in the intronic regions of ACT gene using online servers like FGENESH and FEX [16,17].The genomic, transcript and CCDS sequence of ACT gene was obtained from the NCBI (https://www.ncbi.nlm.nih.gov/gene/12) and FGENESH (http:// www.softberry.com/berry.phtml?topic=fgenesh&group=programs& subgroup=gfind)/FEX (http://www.softberry.com/ berry.phtml?topic=fex&group=programs&subgroup=gfind) analysis were performed. ...
... Helix F has been predicted to unfold at both N and C terminal end during RCL transition, but another hypothesis predicted helix F to be displaced and rearranged after RCL transition [12,[31][32]. Variants in the helix F, strand 6B, helix B and strand 2A in the shutter regions show appreciable increase in the polymerization, however in these variants inhibitory activity against tPA is largely maintained [13,44,45]. Strand 1A is away from the RCL insertion site however it is connected to the helix F through a loop and its N-terminal end connects to s2A ...
... (2019) used this process to modify a periplasmic mercury-binding protein MerP with two green fluorescent protein variants, enhanced cyan fluorescent protein (ECFP) and venus. The resulting protein, MerFS, is a biosensor for mercury II, producing a concentrationdependent ratiometric fluorescence resonance energy transfer (FRET) with micromolar binding affinity [62]. Other biosensors based on FRET signaling include mApple-D6A3 for cadmium II, copper II, and nickel II [63], as well as LaMP1 for lanthanides [64]. ...
... Heparin-binding sites are mainly distributed on the basic D helix, and they can bind pentameric polysaccharides in heparin polysaccharide chains and achieve tight binding with heparin by changing their conformation [45][46][47][48]. Lys 11, Arg 13, Arg46, Arg47, Lys 114, Lys125, and Arg129 have high affinity for heparin [49]. AT also has four glycosylation sites (Asn128, Asn167, Asn187, and Asn224) and three disulfide bonds (Cys40-Cys160, Cys53-Cys127, and Cys279-Cys462). ...
... The mass fraction of water in all hydrogels decreases with the increasing trehalose content, while the volume fraction of polymer  p in all hydrogels remains nearly the same (about 0.11). It is revealed that simple sugar molecules such as trehalose can block polymer formation (42,43). Specifically, trehalose binds to the exposed groups on polymer, which can affect the transition step from native to polymer state, thus making the polymer less polymerogenic. ...
... This could be attributed to the (1) higher platelet count that exerted a strong coagulation effect to form the thrombus more easily (45,46), thus patients were at a high risk of LDVT. (2) The higher APTT indicated poor thromboplastin activity and weak coagulation effect (47,48), which lowered the risk of thrombose and LDVT in patients. Previous studies have also suggested platelet count as a predictor of VTE in patients with cancer (49,50); while APTT is not commonly reported (51). ...
... In 2018, whole-exome sequencing and high-throughput exon sequencing for multiple cases with nephrotic syndrome revealed missense mutations in TNS2 as recessive causative mutations for nephropathy [26]. A Tns2 nonsense mutation (c.1546_1553del, p.Ser516Alafs*19, designated Tns2 nph ), which acts as the equivalent of a null allele, was identified as the recessive causative mutation for proteinuria in an ICGN mouse, a model of chronic kidney disease (CKD), by quantitative trait locus (QTL) analysis and subsequent nucleotide sequencing [27]. ...