Sandbox GGC2

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There are multiple diseases associated with Human Hexokinase 1. It is possible for illness to arise from a deficiency in the protein. A deficiency is a rare autosomal recessive disease in which the <scene name='75/752269/Oliver_leu529/3'>Leucine</scene> and <scene name='75/752269/Oliver_thr680/1'>Threonine</scene> residues in the 529 and the 680 positions are mutated and translated as a Serine. This disease results in nonspherocytic hemolytic anemia <ref>PMID:7655856</ref>.
There are multiple diseases associated with Human Hexokinase 1. It is possible for illness to arise from a deficiency in the protein. A deficiency is a rare autosomal recessive disease in which the <scene name='75/752269/Oliver_leu529/3'>Leucine</scene> and <scene name='75/752269/Oliver_thr680/1'>Threonine</scene> residues in the 529 and the 680 positions are mutated and translated as a Serine. This disease results in nonspherocytic hemolytic anemia <ref>PMID:7655856</ref>.
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Further, diseases of (REWORD THIS) Human Hexokinase can also result in diseases that affect the nervous system. A nervous system disease associated with the protein is neuropathy, '''hereditary motor and sensory, Russe type (HMSNR)''', also known as '''Charcot-Marie-Tooth''' disease. Laboratory studies suggest that this disease is caused by a mutation in a 26 kb range in upstream exons in the Human Hexokinase 1 gene. HMSNR is also autosomal recessive and is usually apparent in the first 10 years of life, characterized by muscular atrophy and impairment in the distal lower limbs. This weakness and atrophy results in those affected by the disease experiencing difficulty walking. HMSNR can later develop into weakness in the distal upper limbs and the proximal lower limbs. It is suspected that this disease is a result of demyelination of the neuronal axon which in turn has negative effects on neuron action potential velocity <ref>PMID:19536174</ref>.
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Also, diseases of Human Hexokinase can also result in diseases that affect the nervous system. A nervous system disease associated with the protein is neuropathy, '''hereditary motor and sensory, Russe type (HMSNR)''', also known as '''Charcot-Marie-Tooth''' disease. Laboratory studies suggest that this disease is caused by a mutation in a 26 kb range in upstream exons in the Human Hexokinase 1 gene. HMSNR is also autosomal recessive and is usually apparent in the first 10 years of life, characterized by muscular atrophy and impairment in the distal lower limbs. This weakness and atrophy results in those affected by the disease experiencing difficulty walking. HMSNR can later develop into weakness in the distal upper limbs and the proximal lower limbs. It is suspected that this disease is a result of demyelination of the neuronal axon which in turn has negative effects on neuron action potential velocity <ref>PMID:19536174</ref>.
Another nervous system disease is a '''neurodevelopmental disorder with visual defects and brain anomalies (NEDVIBA)'''. This disease is found to primarily impact the brain and is characterized by speech delay, intellectual disability, structural brain abnormalities, and visual impairments. The disease is caused by mutations in the 414 position (G → E), the 418 position (K → E), the 445 position (S → L), and in the 457 position (T → M) <ref>PMID:30778173</ref>.
Another nervous system disease is a '''neurodevelopmental disorder with visual defects and brain anomalies (NEDVIBA)'''. This disease is found to primarily impact the brain and is characterized by speech delay, intellectual disability, structural brain abnormalities, and visual impairments. The disease is caused by mutations in the 414 position (G → E), the 418 position (K → E), the 445 position (S → L), and in the 457 position (T → M) <ref>PMID:30778173</ref>.
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There are only a few post-translational modifications that the Human Hexokinase 1 protein undergoes, those being acetylation at the Methionine residue in the 1 position and phosphorylation of the Serine residue in the 337 position, a modification that is also seen in the Rattus norvegicus (Rat) variation of the gene.<ref>PMID:19413330</ref><ref>PMID:22673903</ref>. This serine phosphorylation results in the presence of a phosphoserine.
There are only a few post-translational modifications that the Human Hexokinase 1 protein undergoes, those being acetylation at the Methionine residue in the 1 position and phosphorylation of the Serine residue in the 337 position, a modification that is also seen in the Rattus norvegicus (Rat) variation of the gene.<ref>PMID:19413330</ref><ref>PMID:22673903</ref>. This serine phosphorylation results in the presence of a phosphoserine.
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There are several relevant regions of importance in the Human Hexokinase 1 protein. The N-terminal spanning from residue 1-10, are responsible for the binding interaction between the Human Hexokinase 1 protein and the mitochondria<ref>PMID:1985912</ref>. Further, there are multiple Glucose-6-Phosphate binding domains. These binding domains are seen at residues <scene name='75/752269/Oliver_residues_84-91/1'>84-91</scene>, 413-415, 532-536, and 861-863.
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There are several relevant regions of importance in the Human Hexokinase 1 protein. The N-terminal spanning from residue 1-10, are responsible for the binding interaction between the Human Hexokinase 1 protein and the mitochondria<ref>PMID:1985912</ref>. Further, there are multiple Glucose-6-Phosphate binding domains. These binding domains are seen at residues <scene name='75/752269/Oliver_residues_84-91/1'>84-91</scene>, 413-415, 532-536, and 861-863<ref>PMID:9493266</ref><ref>PMID:10574795</ref><ref>PMID:10686099</ref>.
</StructureSection>
</StructureSection>

Revision as of 23:26, 23 April 2021

1QHA HUMAN HEXOKINASE TYPE I

HUMAN HEXOKINASE TYPE I COMPLEXED WITH ATP ANALOGUE AMP-PNP

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This is a sample scene created with SAT to by Group, and another to make of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

References

  1. ↑ Hanson, R. M., Prilusky, J., Renjian, Z., Nakane, T. and Sussman, J. L. (2013), JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia. Isr. J. Chem., 53:207-216. doi:http://dx.doi.org/10.1002/ijch.201300024
  2. ↑ Herraez A. Biomolecules in the computer: Jmol to the rescue. Biochem Mol Biol Educ. 2006 Jul;34(4):255-61. doi: 10.1002/bmb.2006.494034042644. PMID:21638687 doi:10.1002/bmb.2006.494034042644
  3. ↑ Garfinkel L, Garfinkel D. Magnesium regulation of the glycolytic pathway and the enzymes involved. Magnesium. 1985;4(2-3):60-72. PMID:2931560
  4. ↑ Wolf AJ, Reyes CN, Liang W, Becker C, Shimada K, Wheeler ML, Cho HC, Popescu NI, Coggeshall KM, Arditi M, Underhill DM. Hexokinase Is an Innate Immune Receptor for the Detection of Bacterial Peptidoglycan. Cell. 2016 Jul 28;166(3):624-636. doi: 10.1016/j.cell.2016.05.076. Epub 2016 Jun , 30. PMID:27374331 doi:http://dx.doi.org/10.1016/j.cell.2016.05.076
  5. ↑ Lau E, Kluger H, Varsano T, Lee K, Scheffler I, Rimm DL, Ideker T, Ronai ZA. PKCepsilon promotes oncogenic functions of ATF2 in the nucleus while blocking its apoptotic function at mitochondria. Cell. 2012 Feb 3;148(3):543-55. doi: 10.1016/j.cell.2012.01.016. PMID:22304920 doi:http://dx.doi.org/10.1016/j.cell.2012.01.016
  6. ↑ Bianchi M, Magnani M. Hexokinase mutations that produce nonspherocytic hemolytic anemia. Blood Cells Mol Dis. 1995;21(1):2-8. doi: 10.1006/bcmd.1995.0002. PMID:7655856 doi:http://dx.doi.org/10.1006/bcmd.1995.0002
  7. ↑ Hantke J, Chandler D, King R, Wanders RJ, Angelicheva D, Tournev I, McNamara E, Kwa M, Guergueltcheva V, Kaneva R, Baas F, Kalaydjieva L. A mutation in an alternative untranslated exon of hexokinase 1 associated with hereditary motor and sensory neuropathy -- Russe (HMSNR). Eur J Hum Genet. 2009 Dec;17(12):1606-14. doi: 10.1038/ejhg.2009.99. Epub 2009, Jun 17. PMID:19536174 doi:http://dx.doi.org/10.1038/ejhg.2009.99
  8. ↑ Okur V, Cho MT, van Wijk R, van Oirschot B, Picker J, Coury SA, Grange D, Manwaring L, Krantz I, Muraresku CC, Hulick PJ, May H, Pierce E, Place E, Bujakowska K, Telegrafi A, Douglas G, Monaghan KG, Begtrup A, Wilson A, Retterer K, Anyane-Yeboa K, Chung WK. De novo variants in HK1 associated with neurodevelopmental abnormalities and visual impairment. Eur J Hum Genet. 2019 Jul;27(7):1081-1089. doi: 10.1038/s41431-019-0366-9. Epub, 2019 Feb 18. PMID:30778173 doi:http://dx.doi.org/10.1038/s41431-019-0366-9
  9. ↑ Sullivan LS, Koboldt DC, Bowne SJ, Lang S, Blanton SH, Cadena E, Avery CE, Lewis RA, Webb-Jones K, Wheaton DH, Birch DG, Coussa R, Ren H, Lopez I, Chakarova C, Koenekoop RK, Garcia CA, Fulton RS, Wilson RK, Weinstock GM, Daiger SP. A dominant mutation in hexokinase 1 (HK1) causes retinitis pigmentosa. Invest Ophthalmol Vis Sci. 2014 Sep 4;55(11):7147-58. doi: 10.1167/iovs.14-15419. PMID:25190649 doi:http://dx.doi.org/10.1167/iovs.14-15419
  10. ↑ Wang F, Wang Y, Zhang B, Zhao L, Lyubasyuk V, Wang K, Xu M, Li Y, Wu F, Wen C, Bernstein PS, Lin D, Zhu S, Wang H, Zhang K, Chen R. A missense mutation in HK1 leads to autosomal dominant retinitis pigmentosa. Invest Ophthalmol Vis Sci. 2014 Oct 14;55(11):7159-64. doi:, 10.1167/iovs.14-15520. PMID:25316723 doi:http://dx.doi.org/10.1167/iovs.14-15520
  11. ↑ Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S. Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. PMID:19413330 doi:http://dx.doi.org/10.1021/ac9004309
  12. ↑ Lundby A, Secher A, Lage K, Nordsborg NB, Dmytriyev A, Lundby C, Olsen JV. Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues. Nat Commun. 2012 Jun 6;3:876. doi: 10.1038/ncomms1871. PMID:22673903 doi:http://dx.doi.org/10.1038/ncomms1871
  13. ↑ Magnani M, Serafini G, Bianchi M, Casabianca A, Stocchi V. Human hexokinase type I microheterogeneity is due to different amino-terminal sequences. J Biol Chem. 1991 Jan 5;266(1):502-5. PMID:1985912
  14. ↑ Aleshin AE, Zeng C, Bourenkov GP, Bartunik HD, Fromm HJ, Honzatko RB. The mechanism of regulation of hexokinase: new insights from the crystal structure of recombinant human brain hexokinase complexed with glucose and glucose-6-phosphate. Structure. 1998 Jan 15;6(1):39-50. PMID:9493266
  15. ↑ Rosano C, Sabini E, Rizzi M, Deriu D, Murshudov G, Bianchi M, Serafini G, Magnani M, Bolognesi M. Binding of non-catalytic ATP to human hexokinase I highlights the structural components for enzyme-membrane association control. Structure. 1999 Nov 15;7(11):1427-37. PMID:10574795
  16. ↑ Aleshin AE, Kirby C, Liu X, Bourenkov GP, Bartunik HD, Fromm HJ, Honzatko RB. Crystal structures of mutant monomeric hexokinase I reveal multiple ADP binding sites and conformational changes relevant to allosteric regulation. J Mol Biol. 2000 Mar 3;296(4):1001-15. PMID:10686099 doi:10.1006/jmbi.1999.3494
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