PDBsum entry 1rw3

Transferase, replication

PDB id

1rw3

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Contents

			Protein chain

					443 a.a. *

* Residue conservation analysis

Obsolete entry

PDB id:

1rw3

Links

Name:

Transferase, replication

Title:

The crystal structure of the monomeric reverse transcriptase from moloney murine leukemia virus

Structure:

Pol polyprotein. Chain: a. Fragment: model contains 443 residues, missing residues 1-23,327-334 and 475-671. Engineered: yes. Mutation: yes

Source:

Moloney murine leukemia virus. Organism_taxid: 11801. Gene: pol. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

3.00Å

R-factor:

0.282

R-free:

0.328

Authors:

D.Das,M.M.Georgiadis

Key ref:

D.Das and M.M.Georgiadis (2004). The crystal structure of the monomeric reverse transcriptase from Moloney murine leukemia virus. Structure, 12, 819-829. PubMed id: 15130474 DOI: 10.1016/j.str.2004.02.032

Date:

15-Dec-03

Release date:

25-May-04

PROCHECK

	Headers

	References

Protein chain

P03355 (POL_MLVMS) - Gag-Pol polyprotein from Moloney murine leukemia virus (isolate Shinnick)

Seq: Struc:

Seq: Struc:

Seq: Struc:

Seq: Struc:					1738 a.a. 443 a.a.*

Key:

PfamA domain

Secondary structure

CATH domain

* PDB and UniProt seqs differ at 1 residue position (black cross)



		Enzyme reactions

Enzyme class:

E.C.3.4.23.-, 2.7.7.49 - ?????

[IntEnz] [ExPASy] [KEGG] [BRENDA]

DOI no: 10.1016/j.str.2004.02.032	Structure 12:819-829 (2004)
PubMed id: 15130474

The crystal structure of the monomeric reverse transcriptase from Moloney murine leukemia virus.
D.Das, M.M.Georgiadis.

ABSTRACT

Reverse transcriptases (RTs) are multidomain enzymes of variable architecture that couple both RNA- and DNA-directed DNA polymerase activities with an RNase H activity specific for an RNA:DNA hybrid in order to replicate the single-stranded RNA genome of the retrovirus. Previous structural work has been reported for the heterodimeric HIV-1 and HIV-2 RTs. We now report the first crystal structure of the full-length Moloney murine leukemia virus (MMLV) RT at 3.0 A resolution. The structure reveals a clamp-shaped molecule resulting from the relative positions of the thumb, connection, and RNase H domains that is strikingly different from the HIV-1 RT and provides the first example of a monomeric reverse transcriptase. A comparative analysis with related DNA polymerases suggests a unique trajectory for the template-primer exiting the polymerase active site and provides insights regarding processive DNA synthesis by MMLV RT.

Selected figure(s)



	Figure 2. Figure 2. The Crystal Structure of the MMLV RT and a Comparison with the p66 Subunit of the HIV-1 RT(A) A ribbon rendering of the MMLV RT is shown with the fingers domain in red, palm in blue, thumb in green, connection in yellow, and the RNase H in magenta.(B) A structural comparison of the MMLV RT monomer is shown in the same color scheme as in (A) with the p66 subunit of HIV-1 RT shown in gray. The structures were superimposed using the highly conserved structural elements in the palm domains. In contrast to the rather extended p66 subunit of HIV-1 RT, the MMLV RT is a far more clamp-shaped molecule.

Figure was selected by an automated process.

Literature references that cite this PDB file's key reference

PubMed id

Reference

21338661

J.Xie, P.Zhang, C.Li, Q.Huang, R.Zhou, and T.Peng (2011).
Mechanistic insights into the roles of three linked single-stranded template binding residues of MMLV reverse transcriptase in misincorporation and mispair extension fidelity of DNA synthesis.

Gene, 479, 47-56.

20358252

A.Herschhorn, and A.Hizi (2010).
Retroviral reverse transcriptases.

Cell Mol Life Sci, 67, 2717-2747.

20616052

K.I.Lim, R.Klimczak, J.H.Yu, and D.V.Schaffer (2010).
Specific insertions of zinc finger domains into Gag-Pol yield engineered retroviral vectors with selective integration properties.

Proc Natl Acad Sci U S A, 107, 12475-12480.

20834159

K.Yasukawa, A.Konishi, and K.Inouye (2010).
Effects of organic solvents on the reverse transcription reaction catalyzed by reverse transcriptases from avian myeloblastosis virus and Moloney murine leukemia virus.

Biosci Biotechnol Biochem, 74, 1925-1930.

20139597

M.Mizuno, K.Yasukawa, and K.Inouye (2010).
Insight into the mechanism of the stabilization of moloney murine leukaemia virus reverse transcriptase by eliminating RNase H activity.

Biosci Biotechnol Biochem, 74, 440-442.

20122939

S.J.Schultz, M.Zhang, and J.J.Champoux (2010).
Multiple nucleotide preferences determine cleavage-site recognition by the HIV-1 and M-MuLV RNases H.

J Mol Biol, 397, 161-178.

19056821

B.Arezi, and H.Hogrefe (2009).
Novel mutations in Moloney Murine Leukemia Virus reverse transcriptase increase thermostability through tighter binding to template-primer.

Nucleic Acids Res, 37, 473-481.

19228195

J.J.Champoux, and S.J.Schultz (2009).
Ribonuclease H: properties, substrate specificity and roles in retroviral reverse transcription.

FEBS J, 276, 1506-1516.

19408959

K.Ratcliff, J.Corn, and S.Marqusee (2009).
Structure, stability, and folding of ribonuclease H1 from the moderately thermophilic Chlorobium tepidum: comparison with thermophilic and mesophilic homologues.

Biochemistry, 48, 5890-5898.

PDB code:

3h08

19060310

K.Yasukawa, M.Mizuno, and K.Inouye (2009).
Characterization of Moloney murine leukaemia virus/avian myeloblastosis virus chimeric reverse transcriptases.

J Biochem, 145, 315-324.

19778906

S.J.Schultz, M.Zhang, and J.J.Champoux (2009).
Preferred sequences within a defined cleavage window specify DNA 3' end-directed cleavages by retroviral RNases H.

J Biol Chem, 284, 32225-32238.

19228197

T.Tadokoro, and S.Kanaya (2009).
Ribonuclease H: molecular diversities, substrate binding domains, and catalytic mechanism of the prokaryotic enzymes.

FEBS J, 276, 1482-1493.

18294720

M.L.Coté, and M.J.Roth (2008).
Murine leukemia virus reverse transcriptase: structural comparison with HIV-1 reverse transcriptase.

Virus Res, 134, 186-202.

18261820

S.J.Schultz, and J.J.Champoux (2008).
RNase H activity: structure, specificity, and function in reverse transcription.

Virus Res, 134, 86.

17532359

B.A.Paulson, M.Zhang, S.J.Schultz, and J.J.Champoux (2007).
Substitution of alanine for tyrosine-64 in the fingers subdomain of M-MuLV reverse transcriptase impairs strand displacement synthesis and blocks viral replication in vivo.

Virology, 366, 361-376.

17964265

M.Nowotny, S.A.Gaidamakov, R.Ghirlando, S.M.Cerritelli, R.J.Crouch, and W.Yang (2007).
Structure of human RNase H1 complexed with an RNA/DNA hybrid: insight into HIV reverse transcription.

Mol Cell, 28, 264-276.

PDB codes:

2qk9 2qkb 2qkk

16912289

D.Lim, G.G.Gregorio, C.Bingman, E.Martinez-Hackert, W.A.Hendrickson, and S.P.Goff (2006).
Crystal structure of the moloney murine leukemia virus RNase H domain.

J Virol, 80, 8379-8389.

PDB code:

2hb5

16368688

M.S.Mitchell, J.Tözsér, G.Princler, P.A.Lloyd, A.Auth, and D.Derse (2006).
Synthesis, processing, and composition of the virion-associated HTLV-1 reverse transcriptase.

J Biol Chem, 281, 3964-3971.

15944162

A.Bibillo, D.Lener, A.Tewari, and S.F.Le Grice (2005).
Interaction of the Ty3 reverse transcriptase thumb subdomain with template-primer.

J Biol Chem, 280, 30282-30290.

15852304

G.Tachedjian, J.Radzio, and N.Sluis-Cremer (2005).
Relationship between enzyme activity and dimeric structure of recombinant HIV-1 reverse transcriptase.

Proteins, 60, 5.

15596835

J.L.Mbisa, G.N.Nikolenko, and V.K.Pathak (2005).
Mutations in the RNase H primer grip domain of murine leukemia virus reverse transcriptase decrease efficiency and accuracy of plus-strand DNA transfer.

J Virol, 79, 419-427.

15326591

R.L.Crowther, D.P.Remeta, C.A.Minetti, D.Das, S.P.Montano, and M.M.Georgiadis (2004).
Structural and energetic characterization of nucleic acid-binding to the fingers domain of Moloney murine leukemia virus reverse transcriptase.

Proteins, 57, 15-26.

PDB code:

1nnd

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.