DB code: M00135

RLCP classification	3.103.90021.1120 : Transfer
CATH domain	-.-.-.- :
	3.10.10.10 : HIV Type 1 Reverse Transcriptase; Chain A, domain 1
	3.30.70.270 : Alpha-Beta Plaits	Catalytic domain
	3.30.70.270 : Alpha-Beta Plaits
	3.30.70.270 : Alpha-Beta Plaits
	3.30.420.10 : Nucleotidyltransferase; domain 5	Catalytic domain
	-.-.-.- :
	3.30.420.10 : Nucleotidyltransferase; domain 5	Catalytic domain
	2.30.30.10 : SH3 type barrels.
	-.-.-.- :
E.C.	3.4.23.- 2.7.7.49 3.1.26.4
CSA
M-CSA
MACiE

CATH domain	Related DB codes (homologues)
2.30.30.10 : SH3 type barrels.	M00206 M00146
3.10.10.10 : HIV Type 1 Reverse Transcriptase; Chain A, domain 1	M00206 M00146 M00166
3.30.420.10 : Nucleotidyltransferase; domain 5	M00206 T00252 M00019 M00020 M00055 M00146 M00166 M00173 M00175 M00186
3.30.70.270 : Alpha-Beta Plaits	M00206 M00019 M00146 M00166 M00209

Uniprot Enzyme Name
UniprotKB	Protein name	Synonyms	Contains	RefSeq	MEROPS	Pfam
P03355	Gag-Pol polyprotein	Pr180gag-pol	Matrix protein p15 (MA) RNA-binding phosphoprotein p12 pp12 Capsid protein p30 (CA) Nucleocapsid protein p10 (NC-pol) Protease p14 (PR) EC 3.4.23.- Reverse transcriptase/ribonuclease H p80 (RT) EC 2.7.7.49 EC 2.7.7.7 EC 3.1.26.4 Integrase p46 (IN)	NP_057933.2 (Protein) NC_001501.1 (DNA/RNA sequence)	A02.008 (Aspartic)	PF01140 (Gag_MA) PF01141 (Gag_p12) PF02093 (Gag_p30) PF00075 (RNase_H) PF00665 (rve) PF00077 (RVP) PF00078 (RVT_1) [Graphical View]

KEGG enzyme name

RNA-directed DNA polymerase (EC 2.7.7.49 ) DNA nucleotidyltransferase (RNA-directed) (EC 2.7.7.49 ) reverse transcriptase (EC 2.7.7.49 ) revertase (EC 2.7.7.49 ) RNA-dependent deoxyribonucleate nucleotidyltransferase (EC 2.7.7.49 ) RNA revertase (EC 2.7.7.49 ) RNA-dependent DNA polymerase (EC 2.7.7.49 ) RNA-instructed DNA polymerase (EC 2.7.7.49 ) RT (EC 2.7.7.49 ) calf thymus ribonuclease H (EC 3.1.26.4 ) endoribonuclease H (calf thymus) (EC 3.1.26.4 ) RNase H (EC 3.1.26.4 ) RNA*DNA hybrid ribonucleotidohydrolase (EC 3.1.26.4 ) hybrid ribonuclease (EC 3.1.26.4 ) hybridase (EC 3.1.26.4 ) hybridase (ribonuclease H) (EC 3.1.26.4 ) ribonuclease H (EC 3.1.26.4 ) hybrid nuclease (EC 3.1.26.4 )

UniprotKB: Accession Number	Entry name	Activity	Subunit	Subcellular location	Cofactor
P03355	POL_MLVMO	Endonucleolytic cleavage to 5''- phosphomonoester. Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).

KEGG Pathways
Map code	Pathways	E.C.

Compound table
						Cofactors	Substrates				Products			Intermediates
KEGG-id						C02148	C00677	C00039	C00046	C00001	C00013	C00039	C00960
E.C.							2.7.7.49	2.7.7.49	3.1.26.4	3.1.26.4	2.7.7.49	2.7.7.49	3.1.26.4
Compound						Divalent metal	Deoxynucleoside triphosphate	DNA(n)	RNA	H2O	Pyrophosphate	DNA(n+1)	RNA 5'-phosphate
Type						divalent metal (Ca2+, Mg2+)	nucleotide	nucleic acids	nucleic acids	H2O	phosphate group/phosphate ion	nucleic acids	nucleic acids,phosphate group/phosphate ion
ChEBI										15377 15377	29888 29888
PubChem										22247451 962 22247451 962	1023 21961011 1023 21961011
1d0eA01						Unbound	Unbound	Bound:T-T-T-C-A-T-G-C-A-T-G (chain E), T-T-T-C-A-T-G-C-A-T-G (chain F)	Unbound		Unbound	Unbound	Unbound
1d0eB01						Unbound	Unbound	Unbound	Unbound		Unbound	Unbound	Unbound
1d1uA01						Unbound	Unbound	Bound:C-T-C-G-T-G (chain B), A-C-G-G-C-A-C-G-A-G (chain C)	Unbound		Unbound	Unbound	Unbound
1mmlA01						Unbound	Unbound	Unbound	Unbound		Unbound	Unbound	Unbound
1n4lA01						Unbound	Unbound	Bound:C-T-T-T-T-T-A-A-A-A-G-A-A-A-A-G (chain B), C-T-T-T-T-C-T-T-T-T-A-A-A-A-A-G (chain D)	Unbound		Unbound	Unbound	Unbound
1nndA01						Unbound	Unbound	Unbound	Unbound		Unbound	Unbound	Unbound
1qaiA01						Unbound	Unbound	Bound:C-A-T-G-C-A-T-G (chain D)	Unbound		Unbound	Unbound	Unbound
1qaiB01						Unbound	Unbound	Bound:C-A-T-G-C-A-T-G (chain C)	Unbound		Unbound	Unbound	Unbound
1qajA01						Unbound	Unbound	Bound:C-A-T-G-C-A-T-G (chain C), C-A-T-G-C-A-T-G (chain D)	Unbound		Unbound	Unbound	Unbound
1qajB01						Unbound	Unbound	Unbound	Unbound		Unbound	Unbound	Unbound
1i6jA01						Unbound	Unbound	Bound:G-T-C-G-T-C (chain B), A-C-G-G-G-A-C-G-A-C (chain C)	Unbound		Unbound	Unbound	Unbound
1zttA01						Unbound	Unbound	Bound:C-T-T-A-A-T-T-C (chain B), G-A-A-T-T-A-A-G (chain G)	Unbound		Unbound	Unbound	Unbound
1ztwA01						Unbound	Unbound	Bound:C-T-T-A-A-T-T-C (chain B), G-A-A-T-T-A-A-G (chain G)	Unbound		Unbound	Unbound	Unbound
2fjvA01						Unbound	Unbound	Bound:C-T-T-A-A-T-T-C (chain B), G-A-A-T-T-A-A-G (chain G)	Unbound		Unbound	Unbound	Unbound
2fjwA01						Unbound	Unbound	Bound:C-T-T-G-A-A-T-G (chain B), C-A-T-T-C-A-A-G (chain G)	Unbound		Unbound	Unbound	Unbound
2fjxA01						Unbound	Unbound	Bound:C-T-T-G-A-A-T-G (chain B), C-A-T-T-C-A-A-G (chain G)	Unbound		Unbound	Unbound	Unbound
1rw3A01						Unbound	Unbound	Unbound	Unbound		Unbound	Unbound	Unbound
1d0eA02						Unbound	Unbound	Unbound	Unbound		Unbound	Unbound	Unbound
1d0eB02						Unbound	Unbound	Unbound	Unbound		Unbound	Unbound	Unbound
1d1uA02						Unbound	Unbound	Unbound	Unbound		Unbound	Unbound	Unbound
1mmlA02						Unbound	Unbound	Unbound	Unbound		Unbound	Unbound	Unbound
1n4lA02						Unbound	Unbound	Unbound	Unbound		Unbound	Unbound	Unbound
1nndA02						Unbound	Unbound	Unbound	Unbound		Unbound	Unbound	Unbound
1qaiA02						Unbound	Unbound	Unbound	Unbound		Unbound	Unbound	Unbound
1qaiB02						Unbound	Unbound	Unbound	Unbound		Unbound	Unbound	Unbound
1qajA02						Unbound	Unbound	Unbound	Unbound		Unbound	Unbound	Unbound
1qajB02						Unbound	Unbound	Unbound	Unbound		Unbound	Unbound	Unbound
1i6jA02						Unbound	Unbound	Unbound	Unbound		Unbound	Unbound	Unbound
1zttA02						Unbound	Unbound	Unbound	Unbound		Unbound	Unbound	Unbound
1ztwA02						Unbound	Unbound	Unbound	Unbound		Unbound	Unbound	Unbound
2fjvA02						Unbound	Unbound	Unbound	Unbound		Unbound	Unbound	Unbound
2fjwA02						Unbound	Unbound	Unbound	Unbound		Unbound	Unbound	Unbound
2fjxA02						Unbound	Unbound	Unbound	Unbound		Unbound	Unbound	Unbound
1rw3A02						Unbound	Unbound	Unbound	Unbound		Unbound	Unbound	Unbound
1rw3A03						Unbound	Unbound	Unbound	Unbound		Unbound	Unbound	Unbound
1rw3A04						Unbound	Unbound	Unbound	Unbound		Unbound	Unbound	Unbound

Reference for Active-site residues
resource	references	E.C.
literature [2], [3], [18]

Active-site residues
PDB						Catalytic residues	Cofactor-binding residues	Modified residues	Main-chain involved in catalysis	Comment
1d0eA01
1d0eB01
1d1uA01
1mmlA01
1n4lA01
1nndA01										mutant R116A
1qaiA01
1qaiB01
1qajA01
1qajB01
1i6jA01
1zttA01
1ztwA01
2fjvA01
2fjwA01
2fjxA01
1rw3A01
1d0eA02							ASP 150;ASP 224;ASP 225(Divalent metals binding)		ASP 153;ALA 154
1d0eB02							ASP 150;ASP 224;ASP 225(Divalent metals binding)		ASP 153;ALA 154
1d1uA02							ASP 150;ASP 224;ASP 225(Divalent metals binding)		ASP 153;ALA 154
1mmlA02							ASP 150;ASP 224;ASP 225(Divalent metals binding)		ASP 153;ALA 154
1n4lA02							ASP 150;ASP 224;ASP 225(Divalent metals binding)		ASP 153;ALA 154
1nndA02							ASP 150;ASP 224;ASP 225(Divalent metals binding)		ASP 153;ALA 154
1qaiA02							ASP 150;ASP 224;ASP 225(Divalent metals binding)		ASP 153;ALA 154
1qaiB02							ASP 150;ASP 224;ASP 225(Divalent metals binding)		ASP 153;ALA 154
1qajA02							ASP 150;ASP 224;ASP 225(Divalent metals binding)		ASP 153;ALA 154
1qajB02							ASP 150;ASP 224;ASP 225(Divalent metals binding)		ASP 153;ALA 154
1i6jA02							ASP 150;ASP 224;ASP 225(Divalent metals binding)		ASP 153;ALA 154
1zttA02							ASP 150;ASP 224;ASP 225(Divalent metals binding)		ASP 153;ALA 154
1ztwA02							ASP 150;ASP 224;ASP 225(Divalent metals binding)		ASP 153;ALA 154
2fjvA02							ASP 150;ASP 224;ASP 225(Divalent metals binding)		ASP 153;ALA 154
2fjwA02							ASP 150;ASP 224;ASP 225(Divalent metals binding)		ASP 153;ALA 154
2fjxA02							ASP 150;ASP 224;ASP 225(Divalent metals binding)		ASP 153;ALA 154
1rw3A02							ASP 150;ASP 224;ASP 225(Divalent metals binding)		ASP 153;ALA 154
1rw3A03
1rw3A04

References for Catalytic Mechanism
References	Sections	No. of steps in catalysis
[2]	Fig.5, p.35-36
[3]	p.884-888
[4]	Fig.7, p.5359
[18]	Fig.1, p.14839-14841
[20]	p.824-826

References
[1]
Resource
Comments
Medline ID
PubMed ID	1370551
Journal	J Virol
Year	1992
Volume	66
Pages	615-22
Authors	Telesnitsky A, Blain SW, Goff SP
Title	Defects in Moloney murine leukemia virus replication caused by a reverse transcriptase mutation modeled on the structure of Escherichia coli RNase H.
Related PDB
Related UniProtKB
[3]
Resource
Comments	X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 130-394.
Medline ID	96097395
PubMed ID	8535782
Journal	Structure
Year	1995
Volume	3
Pages	879-92
Authors	Georgiadis MM, Jessen SM, Ogata CM, Telesnitsky A, Goff SP, Hendrickson WA
Title	Mechanistic implications from the structure of a catalytic fragment of Moloney murine leukemia virus reverse transcriptase.
Related PDB	1mml
Related UniProtKB	P03355
[4]
Resource
Comments
Medline ID
PubMed ID	7537090
Journal	Biochemistry
Year	1995
Volume	34
Pages	5351-63
Authors	Patel PH, Jacobo-Molina A, Ding J, Tantillo C, Clark AD Jr, Raag R, Nanni RG, Hughes SH, Arnold E
Title	Insights into DNA polymerization mechanisms from structure and function analysis of HIV-1 reverse transcriptase.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID	9684890
Journal	Protein Sci
Year	1998
Volume	7
Pages	1575-82
Authors	Sun D, Jessen S, Liu C, Liu X, Najmudin S, Georgiadis MM
Title	Cloning, expression, and purification of a catalytic fragment of Moloney murine leukemia virus reverse transcriptase: crystallization of nucleic acid complexes.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID	9741851
Journal	Proteins
Year	1998
Volume	33
Pages	135-43
Authors	Goedken ER, Marqusee S
Title	Folding the ribonuclease H domain of Moloney murine leukemia virus reverse transcriptase requires metal binding or a short N-terminal extension.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID	10600369
Journal	J Mol Biol
Year	1999
Volume	294
Pages	1097-113
Authors	Gao HQ, Sarafianos SG, Arnold E, Hughes SH
Title	Similarities and differences in the RNase H activities of human immunodeficiency virus type 1 reverse transcriptase and Moloney murine leukemia virus reverse transcriptase.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID	10957631
Journal	Acta Crystallogr D Biol Crystallogr
Year	2000
Volume	56
Pages	1120-31
Authors	Cote ML, Yohannan SJ, Georgiadis MM
Title	Use of an N-terminal fragment from moloney murine leukemia virus reverse transcriptase to facilitate crystallization and analysis of a pseudo-16-mer DNA molecule containing G-A mispairs.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID	10913435
Journal	J Biol Chem
Year	2000
Volume	275
Pages	32299-309
Authors	Schultz SJ, Zhang M, Kelleher CD, Champoux JJ
Title	Analysis of plus-strand primer selection, removal, and reutilization by retroviral reverse transcriptases.
Related PDB
Related UniProtKB
[10]
Resource
Comments	X-ray crystallography
Medline ID
PubMed ID	10669612
Journal	J Mol Biol
Year	2000
Volume	296
Pages	613-32
Authors	Najmudin S, Cote ML, Sun D, Yohannan S, Montano SP, Gu J, Georgiadis MM
Title	Crystal structures of an N-terminal fragment from Moloney murine leukemia virus reverse transcriptase complexed with nucleic acid: functional implications for template-primer binding to the fingers domain.
Related PDB	1d0e 1qai 1qaj
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID	11000235
Journal	J Virol
Year	2000
Volume	74
Pages	9629-36
Authors	Pfeiffer JK, Georgiadis MM, Telesnitsky A
Title	Structure-based moloney murine leukemia virus reverse transcriptase mutants with altered intracellular direct-repeat deletion frequencies.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID	10888659
Journal	J Virol
Year	2000
Volume	74
Pages	7171-8
Authors	Svarovskaia ES, Delviks KA, Hwang CK, Pathak VK
Title	Structural determinants of murine leukemia virus reverse transcriptase that affect the frequency of template switching.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID	11526315
Journal	Acta Crystallogr D Biol Crystallogr
Year	2001
Volume	57
Pages	1238-50
Authors	Cote ML, Georgiadis MM
Title	Structure of a pseudo-16-mer DNA with stacked guanines and two G-A mispairs complexed with the N-terminal fragment of Moloney murine leukemia virus reverse transcriptase.
Related PDB	1i6j
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID	11124910
Journal	J Mol Biol
Year	2001
Volume	305
Pages	341-59
Authors	Gu J, Villanueva RA, Snyder CS, Roth MJ, Georgiadis MM
Title	Substitution of Asp114 or Arg116 in the fingers domain of moloney murine leukemia virus reverse transcriptase affects interactions with the template-primer resulting in decreased processivity.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID	11259203
Journal	Virology
Year	2001
Volume	282
Pages	206-13
Authors	Boyer PL, Gao HQ, Frank P, Clark PK, Hughes SH
Title	The basic loop of the RNase H domain of MLV RT is important both for RNase H and for polymerase activity.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID	11237609
Journal	J Mol Biol
Year	2001
Volume	306
Pages	931-43
Authors	Winshell J, Champoux JJ
Title	Structural alterations in the DNA ahead of the primer terminus during displacement synthesis by reverse transcriptases.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID	11433017
Journal	Nucleic Acids Res
Year	2001
Volume	29
Pages	2725-32
Authors	Berthet N, Roupioz Y, Constant JF, Kotera M, Lhomme J
Title	Translesional synthesis on DNA templates containing the 2'-deoxyribonolactone lesion.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID	12475231
Journal	Biochemistry
Year	2002
Volume	41
Pages	14831-42
Authors	Shi Q, Singh K, Srivastava A, Kaushik N, Modak MJ
Title	Lysine 152 of MuLV reverse transcriptase is required for the integrity of the active site.
Related PDB
Related UniProtKB
[19]
Resource
Comments	X-ray crystallography
Medline ID
PubMed ID	12818202
Journal	J Mol Biol
Year	2003
Volume	330
Pages	57-74
Authors	Cote ML, Pflomm M, Georgiadis MM
Title	Staying straight with A-tracts: a DNA analog of the HIV-1 polypurine tract.
Related PDB	1n4l
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID	15130474
Journal	Structure
Year	2004
Volume	12
Pages	819-29
Authors	Das D, Georgiadis MM
Title	The crystal structure of the monomeric reverse transcriptase from Moloney murine leukemia virus.
Related PDB	1rw3
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID	16049022
Journal	Nucleic Acids Res
Year	2005
Volume	33
Pages	4106-16
Authors	Goodwin KD, Long EC, Georgiadis MM
Title	A host-guest approach for determining drug-DNA interactions: an example using netropsin.
Related PDB	1ztt 1ztw
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID	16771498
Journal	J Am Chem Soc
Year	2006
Volume	128
Pages	7846-54
Authors	Goodwin KD, Lewis MA, Tanious FA, Tidwell RR, Wilson WD, Georgiadis MM, Long EC
Title	A high-throughput, high-resolution strategy for the study of site-selective DNA binding agents: Analysis of a "highly twisted" benzimidazole-diamidine.
Related PDB	2fjv 2fjw 2fjx
Related UniProtKB

Comments

This enzyme is composed of the N-terminal protease domain (EC 3.4.23.-), reverse transcriptase domain (E.C. 2.7.7.49), RNase H domain (3.1.26.4), and integrase domain. Only the catalytic domain of the reverse transcriptase (2.7.7.49) has been solved so far. According to the literature [2], [3], [18], the reaction of reverse transcriptase seems to proceed as follows: (1) 3'-hydroxyl group of DNA is activated by a magnesium ion, which is bound to Asp150 and Asp224. (2) The activated 3'-hydroxyl group makes a nucleophilic attack on the alpha-phosphoryl group of dNTP, forming pentacovalent transition state. (3) The transition state is stabilized by both the two magnesium ions. (4) Stabilization by the second magnesium ion and the mainchain amide groups of Asp153 and Ala154 facilitate the leaving of beta- and gamma-phosphate groups.

Created	Updated
2003-07-31	2009-02-26