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Current Topics in Medicinal Chemistry


ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Review Article

A Possible Modulation Mechanism of Intramolecular and Intermolecular Interactions for NCAM Polysialylation and Cell Migration

Author(s): Bo Lu, Xue-Hui Liu, Si-Ming Liao, Zhi-Long Lu, Dong Chen, Frederic A. Troy II, Ri-Bo Huang* and Guo-Ping Zhou*

Volume 19, Issue 25, 2019

Page: [2271 - 2282] Pages: 12

DOI: 10.2174/1568026619666191018094805

Price: $65


Polysialic acid (polySia) is a novel glycan that posttranslationally modifies neural cell adhesion molecules (NCAMs) in mammalian cells. Up-regulation of polySia-NCAM expression or NCAM polysialylation is associated with tumor cell migration and progression in many metastatic cancers and neurocognition. It has been known that two highly homologous mammalian polysialyltransferases (polySTs), ST8Sia II (STX) and ST8Sia IV (PST), can catalyze polysialylation of NCAM, and two polybasic domains, polybasic region (PBR) and polysialyltransferase domain (PSTD) in polySTs play key roles in affecting polyST activity or NCAM polysialylation. However, the molecular mechanisms of NCAM polysialylation and cell migration are still not entirely clear. In this minireview, the recent research results about the intermolecular interactions between the PBR and NCAM, the PSTD and cytidine monophosphate-sialic acid (CMP-Sia), the PSTD and polySia, and as well as the intramolecular interaction between the PBR and the PSTD within the polyST, are summarized. Based on these cooperative interactions, we have built a novel model of NCAM polysialylation and cell migration mechanisms, which may be helpful to design and develop new polysialyltransferase inhibitors.

Keywords: NMR, Sialic acid (Sia), Polysialic acid (polySia), Polysialyltransferases, ST8Sia II (STX), ST8Sia IV (PST), Neural cell adhesion molecules (NCAMs), PSTD, PBR, Cancer metastasis, Phyre2 server.

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Xu, Y.; Wang, Z.; Li, C.; Chou, K.C. iPreny-PseAAC: identify C-terminal cysteine prenylation sites in proteins by incorporating two tiers of sequence couplings into PseAAC. Med. Chem., 2017, 13(6), 544-551.
[] [PMID: 28425870]
Chen, W.; Feng, P.; Yang, H.; Ding, H.; Lin, H.; Chou, K.C. iRNA-3typeA: Identifying 3-types of modification at RNA’s adenosine sites Molecular Therapy. Nucleic Acid, 2018, 11, 468-474.
[PMID: 29858081]
Feng, P.; Yang, H.; Ding, H.; Lin, H.; Chen, W.; Chou, K.C. iDNA6mA-PseKNC: Identifying DNA N6-methyladenosine sites by incorporating nucleotide physicochemical properties into PseKNC. Genomics, 2019, 111(1), 96-102.
Ju, Z.; Wang, S.Y. Prediction of citrullination sites by incorporating k-spaced amino acid pairs into Chou’s general pseudo amino acid composition. Gene, 2018, 664, 78-83.
[] [PMID: 29694908]
Khan, Y.D.; Rasool, N.; Hussain, W.; Khan, S.A.; Chou, K.C. iPhosT-PseAAC: Identify phosphothreonine sites by incorporating sequence statistical moments into PseAAC. Anal. Biochem., 2018, 550, 109-116.
[] [PMID: 29704476]
Sabooh, M.F.; Iqbal, N.; Khan, M.; Khan, M.; Maqbool, H.F. Identifying 5-methylcytosine sites in RNA sequence using composite encoding feature into Chou’s PseKNC. J. Theor. Biol., 2018, 452, 1-9.
[] [PMID: 29727634]
Chou, K.C. An unprecedented revolution in medicinal chemistry driven by the progress of biological science. Curr. Top. Med. Chem., 2017, 17(21), 2337-2358.
[] [PMID: 28413951]
Chou, K.C. Some remarks on protein attribute prediction and pseudo amino acid composition. J. Theor. Biol., 2011, 273(1), 236-247.
[] [PMID: 21168420]
Chen, W.; Lin, H.; Chou, K.C. Pseudo nucleotide composition or PseKNC: an effective formulation for analyzing genomic sequences. Mol. Biosyst., 2015, 11(10), 2620-2634.
[] [PMID: 26099739]
Cheng, X.; Xiao, X.; Chou, K.C. pLoc-mPlant: predict subcellular localization of multi-location plant proteins by incorporating the optimal GO information into general PseAAC. Mol. Biosyst., 2017, 13(9), 1722-1727.
[] [PMID: 28702580]
Cheng, X.; Xiao, X.; Chou, K.C. pLoc-mVirus: predict subcellular localization of multi-location virus proteins via incorporating the optimal GO information into general PseAAC. Gene, 2017, 644, 315-321.
Cheng, X.; Zhao, S.G.; Lin, W.Z.; Xiao, X.; Chou, K.C. pLoc-mAnimal: predict subcellular localization of animal proteins with both single and multiple sites. Bioinformatics, 2017, 33(22), 3524-3531.
[] [PMID: 29036535]
Cheng, X.; Zhao, S.G.; Xiao, X.; Chou, K.C. iATC-mISF: a multi-label classifier for predicting the classes of anatomical therapeutic chemicals. Bioinformatics, 2017, 33, 341-346.
Cheng, X.; Xiao, X.; Chou, K.C. pLoc-mGneg: Predict subcellular localization of Gram-negative bacterial proteins by deep gene ontology learning via general PseAAC. Genomics, 2018, 110, 231-239.
Xiao, X.; Cheng, X.; Su, S.; Nao, Q.; Chou, K.C. pLoc-mGpos: Incorporate key gene ontology information into general PseAAC for predicting subcellular localization of Gram-positive bacterial proteins. Nat. Sci., 2017, 9, 331-349.
Cheng, X.; Xiao, X.; Chou, K.C. pLoc-mEuk: Predict subcellular localization of multi-label eukaryotic proteins by extracting the key GO information into general PseAAC. Genomics, 2018, 110, 50-58.
Cheng, X.; Xiao, X.; Chou, K.C. pLoc-mHum: predict subcellular localization of multi-location human proteins via general PseAAC to winnow out the crucial GO information. Bioinformatics, 2018, 34(9), 1448-1456.
[] [PMID: 29106451]
Xuao, X.; Cheng, X.; Chen, G.; Mao, Q.; Chou, K.C. pLoc_bal-mGpos: predict subcellular localization of Gram-positive bacterial proteins by quasi-balancing training dataset and PseAAC. Genomics, 2019, 111(4), 886-892.
Chou, K.C. Some remarks on predicting multi-label attributes in molecular biosystems. Mol. Biosyst., 2013, 9(6), 1092-1100.
[] [PMID: 23536215]
Chen, W.; Feng, P.M.; Lin, H.; Chou, K.C. iSS-PseDNC: identifying splicing sites using pseudo dinucleotide composition. BiomMed Research Intl. (BMRI), 2014.623149
Feng, P.M.; Chen, W.; Lin, H.; Chou, K.C. iHSP-PseRAAAC: Identifying the heat shock protein families using pseudo reduced amino acid alphabet composition. Anal. Biochem., 2013, 442(1), 118-125.
[] [PMID: 23756733]
Chen, W.; Feng, P.M.; Lin, H.; Chou, K.C. iRSpot-PseDNC: identify recombination spots with pseudo dinucleotide composition. Nucleic Acids Res., 2013, 41(6)e68
[] [PMID: 23303794]
Qiu, W.R.; Xiao, X.; Chou, K.C. iRSpot-TNCPseAAC: Identify recombination spots with trinucleotide composition and pseudo amino acid components. Int. J. Mol. Sci. (IJMS). , 2014, 15, 1746-1766.

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