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866  structures 4448  species 0  interactions 95116  sequences 5396  architectures

Family: RVT_1 (PF00078)

Summary: Reverse transcriptase (RNA-dependent DNA polymerase)

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This is the Wikipedia entry entitled "Reverse transcriptase". More...

Reverse transcriptase Edit Wikipedia article

Reverse transcriptase
(RNA-dependent DNA polymerase)
Reverse transcriptase 3KLF labels.png
Crystallographic structure of HIV-1 reverse transcriptase where the two subunits p51 and p66 are colored and the active sites of polymerase and nuclease are highlighted.[1]
Identifiers
SymbolRVT_1
PfamPF00078
Pfam clanCL0027
InterProIPR000477
PROSITEPS50878
SCOPe1hmv / SUPFAM
CDDcd00304
RNA-directed DNA polymerase
Identifiers
EC number2.7.7.49
CAS number9068-38-6
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO

[2]A reverse transcriptase (RT) is an enzyme used to generate complementary DNA (cDNA) from an RNA template, a process termed reverse transcription. Reverse transcriptases are used by retroviruses to replicate their genomes, by retrotransposon mobile genetic elements to proliferate within the host genome, by eukaryotic cells to extend the telomeres at the ends of their linear chromosomes, and by some non-retroviruses such as the hepatitis B virus, a member of the Hepadnaviridae, which are dsDNA-RT viruses.

Retroviral RT has three sequential biochemical activities: RNA-dependent DNA polymerase activity, ribonuclease H, and DNA-dependent DNA polymerase activity. Collectively, these activities enable the enzyme to convert single-stranded RNA into double-stranded cDNA. In retroviruses and retrotransposons, this cDNA can then integrate into the host genome, from which new RNA copies can be made via host-cell transcription. The same sequence of reactions is widely used in the laboratory to convert RNA to DNA for use in molecular cloning, RNA sequencing, polymerase chain reaction (PCR), or genome analysis.

History

Reverse transcriptases were discovered by Howard Temin at the University of Wisconsin–Madison in Rous sarcoma virions[3] and independently isolated by David Baltimore in 1970 at MIT from two RNA tumour viruses: murine leukemia virus and again Rous sarcoma virus.[2] For their achievements, they shared the 1975 Nobel Prize in Physiology or Medicine (with Renato Dulbecco).

Well-studied reverse transcriptases include:

Function in viruses

Reverse transcriptase is shown with its finger, palm, and thumb regions. The catalytic amino acids of the RNase H active site and the polymerase active site are shown in ball-and-stick form.

The enzymes are encoded and used by viruses that use reverse transcription as a step in the process of replication. Reverse-transcribing RNA viruses, such as retroviruses, use the enzyme to reverse-transcribe their RNA genomes into DNA, which is then integrated into the host genome and replicated along with it. Reverse-transcribing DNA viruses, such as the hepadnaviruses, can allow RNA to serve as a template in assembling and making DNA strands. HIV infects humans with the use of this enzyme. Without reverse transcriptase, the viral genome would not be able to incorporate into the host cell, resulting in failure to replicate.

Process of reverse transcription

Reverse transcriptase creates double-stranded DNA from an RNA template.

In virus species with reverse transcriptase lacking DNA-dependent DNA polymerase activity, creation of double-stranded DNA can possibly be done by host-encoded DNA polymerase δ, mistaking the viral DNA-RNA for a primer and synthesizing a double-stranded DNA by similar mechanism as in primer removal, where the newly synthesized DNA displaces the original RNA template.

The process of reverse transcription is extremely error-prone, and it is during this step that mutations may occur. Such mutations may cause drug resistance.

Retroviral reverse transcription

Mechanism of reverse transcription in HIV. Step numbers will not match up.

Retroviruses, also referred to as class VI ssRNA-RT viruses, are RNA reverse-transcribing viruses with a DNA intermediate. Their genomes consist of two molecules of positive-sense single-stranded RNA with a 5' cap and 3' polyadenylated tail. Examples of retroviruses include the human immunodeficiency virus (HIV) and the human T-lymphotropic virus (HTLV). Creation of double-stranded DNA occurs in the cytosol[6] as a series of these steps:

  1. Lysyl tRNA acts as a primer and hybridizes to a complementary part of the virus RNA genome called the primer binding site or PBS.
  2. Reverse transcriptase then adds DNA nucleotides onto the 3' end of the primer, synthesizing DNA complementary to the U5 (non-coding region) and R region (a direct repeat found at both ends of the RNA molecule) of the viral RNA.
  3. A domain on the reverse transcriptase enzyme called RNAse H degrades the U5 and R regions on the 5’ end of the RNA.
  4. The tRNA primer then "jumps" to the 3’ end of the viral genome, and the newly synthesised DNA strands hybridizes to the complementary R region on the RNA.
  5. The complementary DNA (cDNA) added in (2) is further extended.
  6. The majority of viral RNA is degraded by RNAse H, leaving only the PP sequence.
  7. Synthesis of the second DNA strand begins, using the remaining PP fragment of viral RNA as a primer.
  8. The tRNA primer leaves and a "jump" happens. The PBS from the second strand hybridizes with the complementary PBS on the first strand.
  9. Both strands are extended to form a complete double-stranded DNA copy of the original viral RNA genome, which can then be incorporated into the host's genome by the enzyme integrase.

Creation of double-stranded DNA also involves strand transfer, in which there is a translocation of short DNA product from initial RNA-dependent DNA synthesis to acceptor template regions at the other end of the genome, which are later reached and processed by the reverse transcriptase for its DNA-dependent DNA activity.[7]

Retroviral RNA is arranged in 5’ terminus to 3’ terminus. The site where the primer is annealed to viral RNA is called the primer-binding site (PBS). The RNA 5’end to the PBS site is called U5, and the RNA 3’ end to the PBS is called the leader. The tRNA primer is unwound between 14 and 22 nucleotides and forms a base-paired duplex with the viral RNA at PBS. The fact that the PBS is located near the 5’ terminus of viral RNA is unusual because reverse transcriptase synthesize DNA from 3’ end of the primer in the 5’ to 3’ direction (with respect to the newly synthesized DNA strand). Therefore, the primer and reverse transcriptase must be relocated to 3’ end of viral RNA. In order to accomplish this reposition, multiple steps and various enzymes including DNA polymerase, ribonuclease H(RNase H) and polynucleotide unwinding are needed.[8][9]

The HIV reverse transcriptase also has ribonuclease activity that degrades the viral RNA during the synthesis of cDNA, as well as DNA-dependent DNA polymerase activity that copies the sense cDNA strand into an antisense DNA to form a double-stranded viral DNA intermediate (vDNA).[10]

In cellular life

Self-replicating stretches of eukaryotic genomes known as retrotransposons utilize reverse transcriptase to move from one position in the genome to another via an RNA intermediate. They are found abundantly in the genomes of plants and animals. Telomerase is another reverse transcriptase found in many eukaryotes, including humans, which carries its own RNA template; this RNA is used as a template for DNA replication.[11]

Initial reports of reverse transcriptase in prokaryotes came as far back as 1971 (Beljanski et al., 1971a, 1972). These have since been broadly described as part of bacterial Retrons, distinct sequences that code for reverse transcriptase, and are used in the synthesis of msDNA. In order to initiate synthesis of DNA, a primer is needed. In bacteria, the primer is synthesized during replication.[12]

Valerian Dolja of Oregon State argues that viruses, due to their diversity, have played an evolutionary role in the development of cellular life, with reverse transcriptase playing a central role.[13]

Structure

The reverse transcriptase employs a "right hand" structure similar to that found in other viral nucleic acid polymerases.[14][15] In addition to the transcription function, retroviral reverse transcriptases have a domain belonging to the RNase H family, which is vital to their replication. By degrading the RNA template, it allows the other strand of DNA to be synthesized.[16] Some fragments from the digestion also serves as the primer for the DNA polymerase (either the same enzyme or a host protein), responsible for making the other (plus) strand.[14]

Replication fidelity

There are three different replication systems during the life cycle of a retrovirus. First of all, the reverse transcriptase synthesizes viral DNA from viral RNA, and then from newly made complementary DNA strand. The second replication process occurs when host cellular DNA polymerase replicates the integrated viral DNA. Lastly, RNA polymerase II transcribes the proviral DNA into RNA, which will be packed into virions. Therefore, mutation can occur during one or all of these replication steps.[17]

Reverse transcriptase has a high error rate when transcribing RNA into DNA since, unlike most other DNA polymerases, it has no proofreading ability. This high error rate allows mutations to accumulate at an accelerated rate relative to proofread forms of replication. The commercially available reverse transcriptases produced by Promega are quoted by their manuals as having error rates in the range of 1 in 17,000 bases for AMV and 1 in 30,000 bases for M-MLV.[18]

Other than creating single-nucleotide polymorphisms, reverse transcriptases have also been shown to be involved in processes such as transcript fusions, exon shuffling and creating artificial antisense transcripts.[19][20] It has been speculated that this template switching activity of reverse transcriptase, which can be demonstrated completely in vivo, may have been one of the causes for finding several thousand unannotated transcripts in the genomes of model organisms.[21]

Applications

The molecular structure of zidovudine (AZT), a drug used to inhibit HIV reverse transcriptase

Antiviral drugs

As HIV uses reverse transcriptase to copy its genetic material and generate new viruses (part of a retrovirus proliferation circle), specific drugs have been designed to disrupt the process and thereby suppress its growth. Collectively, these drugs are known as reverse-transcriptase inhibitors and include the nucleoside and nucleotide analogues zidovudine (trade name Retrovir), lamivudine (Epivir) and tenofovir (Viread), as well as non-nucleoside inhibitors, such as nevirapine (Viramune).

Molecular biology

Reverse transcriptase is commonly used in research to apply the polymerase chain reaction technique to RNA in a technique called reverse transcription polymerase chain reaction (RT-PCR). The classical PCR technique can be applied only to DNA strands, but, with the help of reverse transcriptase, RNA can be transcribed into DNA, thus making PCR analysis of RNA molecules possible. Reverse transcriptase is used also to create cDNA libraries from mRNA. The commercial availability of reverse transcriptase greatly improved knowledge in the area of molecular biology, as, along with other enzymes, it allowed scientists to clone, sequence, and characterise RNA.

Reverse transcriptase has also been employed in insulin production. By inserting eukaryotic mRNA for insulin production along with reverse transcriptase into bacteria, the mRNA could be inserted into the prokaryote's genome. Large amounts of insulin can then be created, sidestepping the need to harvest pig pancreas and other such traditional sources. Directly inserting eukaryotic DNA into bacteria would not work because it carries introns, so would not translate successfully using the bacterial ribosomes. Processing in the eukaryotic cell during mRNA production removes these introns to provide a suitable template. Reverse transcriptase converted this edited RNA back into DNA so it could be incorporated in the genome.

See also

References

  1. ^ PDB: 3KLF​; Tu X, Das K, Han Q, Bauman JD, Clark AD, Hou X, Frenkel YV, Gaffney BL, Jones RA, Boyer PL, Hughes SH, Sarafianos SG, Arnold E (October 2010). "Structural basis of HIV-1 resistance to AZT by excision". Nature Structural & Molecular Biology. 17 (10): 1202–9. doi:10.1038/nsmb.1908. PMC 2987654. PMID 20852643.
  2. ^ a b Baltimore D (June 1970). "RNA-dependent DNA polymerase in virions of RNA tumour viruses". Nature. 226 (5252): 1209–11. doi:10.1038/2261209a0. PMID 4316300.
  3. ^ Temin HM, Mizutani S (June 1970). "RNA-dependent DNA polymerase in virions of Rous sarcoma virus". Nature. 226 (5252): 1211–3. doi:10.1038/2261211a0. PMID 4316301.
  4. ^ Ferris AL, Hizi A, Showalter SD, Pichuantes S, Babe L, Craik CS, Hughes SH (April 1990). "Immunologic and proteolytic analysis of HIV-1 reverse transcriptase structure" (PDF). Virology. 175 (2): 456–64. doi:10.1016/0042-6822(90)90430-y. PMID 1691562.
  5. ^ a b Konishi A, Yasukawa K, Inouye K (July 2012). "Improving the thermal stability of avian myeloblastosis virus reverse transcriptase α-subunit by site-directed mutagenesis" (PDF). Biotechnology Letters. 34 (7): 1209–15. doi:10.1007/s10529-012-0904-9. PMID 22426840.
  6. ^ Bio-Medicine.org - Retrovirus Retrieved on 17 Feb, 2009
  7. ^ Telesnitsky A, Goff SP (1993). "Strong-stop strand transfer during reverse transcription". In Skalka MA, Goff SP (eds.). Reverse transcriptase (1st ed.). New York: Cold Spring Harbor. p. 49. ISBN 978-0-87969-382-4.
  8. ^ Bernstein A, Weiss R, Tooze J (1985). "RNA tumor viruses". Molecular Biology of Tumor Viruses (2nd ed.). Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory.
  9. ^ Moelling K, Broecker F (April 2015). "The reverse transcriptase-RNase H: from viruses to antiviral defense". Annals of the New York Academy of Sciences. 1341: 126–35. doi:10.1111/nyas.12668. PMID 25703292.
  10. ^ Kaiser GE (January 2008). "The Life Cycle of HIV". Doc Kaiser's Microbiology Home Page. Community College of Baltimore Count. Archived from the original on 2010-07-26.
  11. ^ Krieger M, Scott MP, Matsudaira PT, Lodish HF, Darnell JE, Zipursky L, Kaiser C, Berk A (2004). Molecular cell biology. New York: W.H. Freeman and CO. ISBN 978-0-7167-4366-8.
  12. ^ Hurwitz J, Leis JP (January 1972). "RNA-dependent DNA polymerase activity of RNA tumor viruses. I. Directing influence of DNA in the reaction". Journal of Virology. 9 (1): 116–29. PMC 356270. PMID 4333538.
  13. ^ Arnold C (17 July 2014). "Could Giant Viruses Be the Origin of Life on Earth?". National Geographic. Retrieved 29 May 2016.
  14. ^ a b Sarafianos SG, Marchand B, Das K, Himmel DM, Parniak MA, Hughes SH, Arnold E (January 2009). "Structure and function of HIV-1 reverse transcriptase: molecular mechanisms of polymerization and inhibition". Journal of Molecular Biology. 385 (3): 693–713. doi:10.1016/j.jmb.2008.10.071. PMC 2881421. PMID 19022262.
  15. ^ Hansen JL, Long AM, Schultz SC (August 1997). "Structure of the RNA-dependent RNA polymerase of poliovirus". Structure. 5 (8): 1109–22. doi:10.1016/S0969-2126(97)00261-X. PMID 9309225.
  16. ^ Schultz SJ, Champoux JJ (June 2008). "RNase H activity: structure, specificity, and function in reverse transcription". Virus Research. 134 (1–2): 86–103. doi:10.1016/j.virusres.2007.12.007. PMC 2464458. PMID 18261820.
  17. ^ Bbenek K, Kunkel AT (1993). "The fidelity of retroviral reverse transcriptases". In Skalka MA, Goff PS (eds.). Reverse transcriptase. New York: Cold Spring Harbor Laboratory Press. p. 85. ISBN 978-0-87969-382-4.
  18. ^ "Promega kit instruction manual" (PDF). 1999. Archived from the original (PDF) on 2006-11-21.
  19. ^ Houseley J, Tollervey D (August 2010). "Apparent non-canonical trans-splicing is generated by reverse transcriptase in vitro". PLOS ONE. 5 (8): e12271. doi:10.1371/journal.pone.0012271. PMC 2923612. PMID 20805885.
  20. ^ Zeng XC, Wang SX (June 2002). "Evidence that BmTXK beta-BmKCT cDNA from Chinese scorpion Buthus martensii Karsch is an artifact generated in the reverse transcription process". FEBS Letters. 520 (1–3): 183–4, author reply 185. doi:10.1016/S0014-5793(02)02812-0. PMID 12044895.
  21. ^ van Bakel H, Nislow C, Blencowe BJ, Hughes TR (2011). "Response to "The Reality of Pervasive Transcription"". PLoS Biology. 9 (7): e1001102. doi:10.1371/journal.pbio.1001102. PMC 3134445.

External links

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Reverse transcriptase (RNA-dependent DNA polymerase) Provide feedback

A reverse transcriptase gene is usually indicative of a mobile element such as a retrotransposon or retrovirus. Reverse transcriptases occur in a variety of mobile elements, including retrotransposons, retroviruses, group II introns, bacterial msDNAs, hepadnaviruses, and caulimoviruses.

Literature references

  1. Xiong Y, Eickbush TH; , EMBO J 1990;9:3353-3362.: Origin and evolution of retroelements based upon their reverse transcriptase sequences. PUBMED:1698615 EPMC:1698615


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000477

The use of an RNA template to produce DNA, for integration into the host genome and exploitation of a host cell, is a strategy employed in the replication of retroid elements, such as the retroviruses and bacterial retrons. The enzyme catalysing polymerisation is an RNA-directed DNA-polymerase, or reverse trancriptase (RT) ( EC ). Reverse transcriptase occurs in a variety of mobile elements, including retrotransposons, retroviruses, group II introns [ PUBMED:12758069 ], bacterial msDNAs, hepadnaviruses, and caulimoviruses.

Retroviral reverse transcriptase is synthesised as part of the POL polyprotein that contains; an aspartyl protease, a reverse transcriptase, RNase H and integrase. POL polyprotein undergoes specific enzymatic cleavage to yield the mature proteins. The discovery of retroelements in the prokaryotes raises intriguing questions concerning their roles in bacteria and the origin and evolution of reverse transcriptases and whether the bacterial reverse transcriptases are older than eukaryotic reverse transcriptases [ PUBMED:8828137 ].

Several crystal structures of the reverse transcriptase (RT) domain have been determined [ PUBMED:1377403 ].

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan RdRP (CL0027), which has the following description:

This clan represents the replicative RNA dependent RNA polymerase. from a variety of RNA viruses [1].

The clan contains the following 11 members:

Birna_RdRp DUF6451 Flavi_NS5 Mitovir_RNA_pol RdRP_1 RdRP_2 RdRP_3 RdRP_4 RVT_1 RVT_2 Viral_RdRp_C

Alignments

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  Seed
(69)
Full
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Representative proteomes UniProt
(609756)
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(33990)
RP35
(58756)
RP55
(89535)
RP75
(106670)
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

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HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Published_alignment and HMM_iterative_training
Previous IDs: rvt; RVT;
Type: Domain
Sequence Ontology: SO:0000417
Author: Eddy SR
Number in seed: 69
Number in full: 95116
Average length of the domain: 170.60 aa
Average identity of full alignment: 16 %
Average coverage of the sequence by the domain: 25.45 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 29.6 29.6
Trusted cut-off 29.6 29.6
Noise cut-off 29.5 29.5
Model length: 222
Family (HMM) version: 29
Download: download the raw HMM for this family

Species distribution

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Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the RVT_1 domain has been found. There are 866 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A0G2JUM9 View 3D Structure Click here
A0A0G2JVY3 View 3D Structure Click here
A0A0G2JX86 View 3D Structure Click here
A0A0G2JZP4 View 3D Structure Click here
A0A0G2K076 View 3D Structure Click here
A0A0G2K4R8 View 3D Structure Click here
A0A0G2K5R1 View 3D Structure Click here
A0A0G2K5Z0 View 3D Structure Click here
A0A0G2K614 View 3D Structure Click here
A0A0G2K7H3 View 3D Structure Click here
A0A0G2KB86 View 3D Structure Click here
A0A0G2KBC8 View 3D Structure Click here
A0A0G2KI12 View 3D Structure Click here
A0A0G2KJS8 View 3D Structure Click here
A0A0G2KJV6 View 3D Structure Click here
A0A0G2KL83 View 3D Structure Click here
A0A0G2KM65 View 3D Structure Click here
A0A0G2KS01 View 3D Structure Click here
A0A0G2KTU9 View 3D Structure Click here
A0A0G2KV08 View 3D Structure Click here
A0A0G2KVG6 View 3D Structure Click here
A0A0G2KYC1 View 3D Structure Click here
A0A0G2L0G5 View 3D Structure Click here
A0A0G2L1S3 View 3D Structure Click here
A0A0G2L2B6 View 3D Structure Click here
A0A0G2L3N0 View 3D Structure Click here
A0A0G2L3T5 View 3D Structure Click here
A0A0G2L6S5 View 3D Structure Click here
A0A0G2L7N4 View 3D Structure Click here
A0A0G2L818 View 3D Structure Click here
A0A0G2LA86 View 3D Structure Click here
A0A0G2LAH6 View 3D Structure Click here
A0A0N7KKH0 View 3D Structure Click here
A0A0N7KTK3 View 3D Structure Click here
A0A0P0UYZ2 View 3D Structure Click here
A0A0P0W1C4 View 3D Structure Click here
A0A0P0W7K0 View 3D Structure Click here
A0A0P0WX53 View 3D Structure Click here
A0A0P0YB17 View 3D Structure Click here
A0A0R0EG68 View 3D Structure Click here
A0A0R0F9J4 View 3D Structure Click here
A0A0R0HQQ7 View 3D Structure Click here
A0A0R0IML2 View 3D Structure Click here
A0A0R4ISL7 View 3D Structure Click here
A0A0R4IYX4 View 3D Structure Click here
A0A1D6EK93 View 3D Structure Click here
A0A1D6EKM9 View 3D Structure Click here
A0A1D6ERU1 View 3D Structure Click here
A0A1D6FEM7 View 3D Structure Click here
A0A1D6FII7 View 3D Structure Click here
A0A1D6FJU8 View 3D Structure Click here
A0A1D6FKK2 View 3D Structure Click here
A0A1D6FM79 View 3D Structure Click here
A0A1D6FSW8 View 3D Structure Click here
A0A1D6FUZ4 View 3D Structure Click here
A0A1D6FV14 View 3D Structure Click here
A0A1D6G0V4 View 3D Structure Click here
A0A1D6G503 View 3D Structure Click here
A0A1D6GGM0 View 3D Structure Click here
A0A1D6GHI2 View 3D Structure Click here
A0A1D6GIN4 View 3D Structure Click here
A0A1D6GN15 View 3D Structure Click here
A0A1D6GRX4 View 3D Structure Click here
A0A1D6GU15 View 3D Structure Click here
A0A1D6GU15 View 3D Structure Click here
A0A1D6GYF0 View 3D Structure Click here
A0A1D6H1V1 View 3D Structure Click here
A0A1D6H3M4 View 3D Structure Click here
A0A1D6H4H2 View 3D Structure Click here
A0A1D6H871 View 3D Structure Click here
A0A1D6HDF4 View 3D Structure Click here
A0A1D6HE72 View 3D Structure Click here
A0A1D6HX90 View 3D Structure Click here
A0A1D6I351 View 3D Structure Click here
A0A1D6I601 View 3D Structure Click here
A0A1D6I607 View 3D Structure Click here
A0A1D6I7A1 View 3D Structure Click here
A0A1D6IEH9 View 3D Structure Click here
A0A1D6IGM0 View 3D Structure Click here
A0A1D6IMH2 View 3D Structure Click here
A0A1D6IPM0 View 3D Structure Click here
A0A1D6IXS6 View 3D Structure Click here
A0A1D6J4S8 View 3D Structure Click here
A0A1D6J4U6 View 3D Structure Click here
A0A1D6J596 View 3D Structure Click here
A0A1D6J5H5 View 3D Structure Click here
A0A1D6J6A3 View 3D Structure Click here
A0A1D6JF34 View 3D Structure Click here
A0A1D6JIM9 View 3D Structure Click here
A0A1D6JJN9 View 3D Structure Click here
A0A1D6JQ10 View 3D Structure Click here
A0A1D6K060 View 3D Structure Click here
A0A1D6K3M7 View 3D Structure Click here
A0A1D6KG90 View 3D Structure Click here
A0A1D6KKX4 View 3D Structure Click here
A0A1D6KLY6 View 3D Structure Click here
A0A1D6KNX4 View 3D Structure Click here
A0A1D6KUQ6 View 3D Structure Click here
A0A1D6KVT7 View 3D Structure Click here
A0A1D6KWI6 View 3D Structure Click here
A0A1D6KWJ1 View 3D Structure Click here
A0A1D6KX28 View 3D Structure Click here
A0A1D6KX85 View 3D Structure Click here
A0A1D6L213 View 3D Structure Click here
A0A1D6L6H0 View 3D Structure Click here
A0A1D6LAQ1 View 3D Structure Click here
A0A1D6LC02 View 3D Structure Click here
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