Reverse transcriptase: Difference between revisions
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This ''hand-like'' <scene name='Reverse_transcriptase/Chains/2'>heterodimer</scene> protein that has an usual length of 1000 residues (560 in Chain A and 440 for B), the third of them involved in alpha helical and almost a quarter in beta sheets, showing α+β <scene name='Reverse_transcriptase/Secondary/2'>secondary structure</scene> domains; <scene name='Reverse_transcriptase/Chaina/2'>Chain A</scene> has an usual weight of 66KDa whereas <scene name='Reverse_transcriptase/Chainb/2'>Chain B</scene> is around 51KDa, those monomers are derived from the same gen but p51 lacks the aminoacids of one active site and has a different tertiary structure conformation compared with p66, for this reason is totally inactive. [http://www.sciencemag.org.silk.library.umass.edu:2048/cgi/content/abstract/sci;256/5065/1783?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&andorexacttitleabs=and&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&volume=256&firstpage=1783&resourcetype=HWCIT] | This ''hand-like'' <scene name='Reverse_transcriptase/Chains/2'>heterodimer</scene> protein that has an usual length of 1000 residues (560 in Chain A and 440 for B), the third of them involved in alpha helical and almost a quarter in beta sheets, showing α+β <scene name='Reverse_transcriptase/Secondary/2'>secondary structure</scene> domains; <scene name='Reverse_transcriptase/Chaina/2'>Chain A</scene> has an usual weight of 66KDa whereas <scene name='Reverse_transcriptase/Chainb/2'>Chain B</scene> is around 51KDa, those monomers are derived from the same gen but p51 lacks the aminoacids of one active site and has a different tertiary structure conformation compared with p66, for this reason is totally inactive. [http://www.sciencemag.org.silk.library.umass.edu:2048/cgi/content/abstract/sci;256/5065/1783?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&andorexacttitleabs=and&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&volume=256&firstpage=1783&resourcetype=HWCIT] | ||
{{Clear}} | {{Clear}} | ||
==Function== | ==Function== | ||
{{STRUCTURE_3hvt| PDB=3jyt | SCENE='Reverse_transcriptase/Initial/1' size='[450,338]' align='right' frame='true' caption='Reverse Transcriptase' }} | {{STRUCTURE_3hvt| PDB=3jyt | SCENE='Reverse_transcriptase/Initial/1' size='[450,338]' align='right' frame='true' caption='Reverse Transcriptase' }} | ||
As a RNA-dependent DNA Polymerase, is able to recognize the initial RNA, transcribe it to ssDNA, cleave the remaining RNA and then build up the dsDNA, to do this the protein has two active catalytic zones. Chain A has the <scene name='Reverse_transcriptase/Fingers/ | As a RNA-dependent DNA Polymerase, is able to recognize the initial RNA, transcribe it to ssDNA, cleave the remaining RNA and then build up the dsDNA, to do this the protein has two active catalytic zones. Chain A has the <scene name='Reverse_transcriptase/Fingers/4'>Polymerase active site</scene> that consist of two ''finger-like'' domains, one of them recognizes the initial nucleic acid by h-bonds interactions with phosphate groups of the side chains, then both domains make a conformational change closing the recognition hole to allow the second domain with the support a <scene name='Reverse_transcriptase/Magnesium/2'>Magnesium ion</scene> coordination system, begin the transcription process adding the specific DNA nucleotides; this change is allowed by a <scene name='Reverse_transcriptase/Flexible/2'>flexible zone</scene> between the two previous domains that is used as a common pharmaceutical target site in order to prevent this change and by this way inhibit the activity, but this one is the only zone of the Chain A that has non-conserved aminoacids giving the virus more drug resistance. [http://consurfdb.tau.ac.il/chain_selection.php?pdb_ID=1JLB] | ||
As the same rate that the polymerization process occurs, the other active site known as the <scene name='Reverse_transcriptase/Rnase/ | As the same rate that the polymerization process occurs, the other active site known as the <scene name='Reverse_transcriptase/Rnase/2'>Ribonuclease H domain</scene>, cleaves the RNA releasing the ssDNA that comes again trough the Polymerase active site to become dsDNA (all this with a <scene name='Reverse_transcriptase/Magnesium2/2'>second Magnesium</scene> coordinative system, that allows non-specific recognition, just with phosphates). Finally Chain B despite of the similar aminoacid sequence with Chain A has no enzyme activity, possibly its function is to stabilize and communicate both active sites, this varying the length between them in order to synchronize both functions. | ||
This seems to be the most general idea of the mechanism of action of Reverse Transcriptase, however the process remains unclear and new approaches are being reported. [http://www.nature.com/nature/journal/v453/n7192/full/nature06941.html] | This seems to be the most general idea of the mechanism of action of Reverse Transcriptase, however the process remains unclear and new approaches are being reported. [http://www.nature.com/nature/journal/v453/n7192/full/nature06941.html] | ||
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* Molecule of the Month (09/2002) at [http://www.pdb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb33_1.html RCSB Protein Data Bank] | * Molecule of the Month (09/2002) at [http://www.pdb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb33_1.html RCSB Protein Data Bank] | ||
* List of Reverse Transcriptase articles at [http://www.proteopedia.org/wiki/index.php/Category:Reverse_transcriptase Proteopedia] and at [http://www.pdb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb33_report.html RCSB Protein Data Bank] | * List of Reverse Transcriptase articles at [http://www.proteopedia.org/wiki/index.php/Category:Reverse_transcriptase Proteopedia] and at [http://www.pdb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb33_report.html RCSB Protein Data Bank] | ||
* | * Model of Reverse Transcriptase as one of the [[CBI Molecules|CBI Molecules]] on the [http://www.molecularplayground.org Molecular Playground] | ||
