4r5p

Crystal structure of HIV-1 reverse transcriptase (RT) with DNA and a nucleoside triphosphate mimic alpha-carboxy nucleoside phosphonate inhibitor

Method: X-RAY DIFFRACTION

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1. Protein Identity and Related Structures Protein Identity & Related Structures

HIV-1 reverse transcriptase, p66 subunit

Human immunodeficiency virus type 1

State in the Current Structure

Assembly	Physical composition	Protein state	Molecular copy count	Associated components	Data consistency
1	Protein–DNA	Homooligomer	Protein 2 DNA 2 其他Polymer 1	5'-D(TPGPGPAPCPGPGPCPGPCPCPCPGPAPAPCPAPGPGPGPAPCPTPG)-3' × 1 5'-D(CPAPGPTPCPCPCPTPGPTPTPCPGPGP(MRG)PCPGPCPCPG)-3' × 1 beta-D-fructofuranose-(2-1)-alpha-D-glucopyranose × 1 MAGNESIUM ION × 3 [(1R)-2-methoxy-1-{[(1S,3R)-3-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)cyclopentyl]oxy}-2-oxoethyl]phosphonic acid × 1 water × 2	Review required
2	Protein–DNA	Homooligomer	Protein 2 DNA 2 其他Polymer 1	5'-D(TPGPGPAPCPGPGPCPGPCPCPCPGPAPAPCPAPGPGPGPAPCPTPG)-3' × 1 5'-D(CPAPGPTPCPCPCPTPGPTPTPCPGPGP(MRG)PCPGPCPCPG)-3' × 1 beta-D-fructofuranose-(2-1)-alpha-D-glucopyranose × 1 MAGNESIUM ION × 3 [(1R)-2-methoxy-1-{[(1S,3R)-3-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)cyclopentyl]oxy}-2-oxoethyl]phosphonic acid × 1 SULFATE ION × 1 water × 2	Review required

Other States of the Same Protein in the Database

View Construct and Data Evidence

UniProt name	POL_HV1B1
Isoform	—
PDB entities	1, 2
Chains and sequence ranges	Author chain A； PDBConstruct 3–556； UniProt 600–1153 Author chain C； PDBConstruct 3–556； UniProt 600–1153 Author chain B； PDBConstruct 1–428； UniProt 600–1027 Author chain D； PDBConstruct 1–428； UniProt 600–1027

The page prioritizes protein identity, the current assembly, associated components, oligomeric state and cross-PDB links. Chain mapping and sequence ranges are retained as data evidence. Internal IDs, import timestamps and assembly operation expressions are maintenance fields and are not shown here.

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2. Structure Basics 2. Structure Basics

Entry ID entry_id	4r5p
Deposition date deposition_date	2014-08-21
Structure title title	Crystal structure of HIV-1 reverse transcriptase (RT) with DNA and a nucleoside triphosphate mimic alpha-carboxy nucleoside phosphonate inhibitor
Keywords keywords	;Zidovudine, RT-DNA complex, AIDS, DNA-directed DNA polymerase, RN lipoprotein, HIV, metal-binding, alpha-CNP, ribonuclease H, RNAse H, A-CNP, multifunctional enzyme, nucleotidyltransferase, RNA-directed polymerase, TRANSFERASE, HYDROLASE-DNA-INHIBITOR complex ;; TRANSFERASE, HYDROLASE/DNA/INHIBITOR
Experimental Method method	X-RAY DIFFRACTION

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3. Official assembly/model SAXS Official SAXS Profiles

This page reads only the latest assembly calculations. Every curve maps to an explicit PDB entry, official biological assembly and coordinate model.

4r5p__assembly_1__model_1

Assembly 1 · Model 1 · CRYSOL 4.1.3-1-20251215 (887e7ef)

Download this curve (.dat)

4r5p__assembly_1__model_1 | I(q)

100 plotted points; both axes use logarithmic scales.

4r5p__assembly_1__model_1 | P(r) · Pending

P(r) will be calculated and displayed separately for the same assembly/model.

Rg（Guinier）	33.38 Å
Rg (electron density)	33.17 Å
Total Rg	33.77 Å
Atom count	8853
Residues	1010
Excluded volume	156240 Å³
Maximum q	0.500 Å⁻¹

Assembly	Model	Structure unit	Oligomeric description	Status	CRYSOL	Actions
1	1	`4r5p__assembly_1__model_1`	tetrameric （4）	Success	4.1.3-1-20251215 (887e7ef)	View Download
2	1	`4r5p__assembly_2__model_1`	tetrameric （4）	Success	4.1.3-1-20251215 (887e7ef)	View Download

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4. Crystallography and Experiment 4. Crystallography & Experiment

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5. Entities and Polymers Entities & Polymers (9)

Entity 1 Entity 1 polymer

Description description	HIV-1 reverse transcriptase, p66 subunit
Molecular weight formula_weight	64022.4 kDa
EC 编号 ec_number	2.7.7.49, 2.7.7.7, 3.1.26.13, 3.1.13.2
Mutation mutation	Q258C, C280S, D498N
Source method src_method	man
Copy count entity_count	2

Polymer Polymer

Polymer type type	polypeptide(L)
Chain IDs strand_id	A,C
Atom count atom_count	17714

MVPISPIETVPVKLKPGMDGPKVKQWPLTEEKIKALVEICTEMEKEGKISKIGPENPYNTPVFAIKKKDSTKWRKLVDFRELNKRTQDFWEVQLGIPHPAGLKKKKSVTVLDVGDAYFSVPLDEDFRKYTAFTIPSINNETPGIRYQYNVLPQGWKGSPAIFQSSMTKILEPFKKQNPDIVIYQYMDDLYVGSDLEIGQHRTKIEELRQHLLRWGLTTPDKKHQKEPPFLWMGYELHPDKWTVQPIVLPEKDSWTVNDICKLVGKLNWASQIYPGIKVRQLSKLLRGTKALTEVIPLTEEAELELAENREILKEPVHGVYYDPSKDLIAEIQKQGQGQWTYQIYQEPFKNLKTGKYARMRGAHTNDVKQLTEAVQKITTESIVIWGKTPKFKLPIQKETWETWWTEYWQATWIPEWEFVNTPPLVKLWYQLEKEPIVGAETFYVDGAANRETKLGKAGYVTNKGRQKVVPLTNTTNQKTELQAIYLALQDSGLEVNIVTNSQYALGIIQAQPDKSESELVNQIIEQLIKKEKVYLAWVPAHKGIGGNEQVDKLVSA

Source Source

Source organism organism	Human immunodeficiency virus type 1
Common name common_name	HIV-1
NCBI taxonomy ID ncbi_taxonomy_id	11678
Host organism host_organism	Escherichia coli

Entity 2 Entity 2 polymer

Description description	HIV-1 reverse transcriptase, p51 subunit
Molecular weight formula_weight	50039.5 kDa
EC 编号 ec_number	2.7.7.49, 2.7.7.7
Mutation mutation	C280S
Source method src_method	man
Copy count entity_count	2

Polymer Polymer

Polymer type type	polypeptide(L)
Chain IDs strand_id	B,D

PISPIETVPVKLKPGMDGPKVKQWPLTEEKIKALVEICTEMEKEGKISKIGPENPYNTPVFAIKKKDSTKWRKLVDFRELNKRTQDFWEVQLGIPHPAGLKKKKSVTVLDVGDAYFSVPLDEDFRKYTAFTIPSINNETPGIRYQYNVLPQGWKGSPAIFQSSMTKILEPFKKQNPDIVIYQYMDDLYVGSDLEIGQHRTKIEELRQHLLRWGLTTPDKKHQKEPPFLWMGYELHPDKWTVQPIVLPEKDSWTVNDIQKLVGKLNWASQIYPGIKVRQLSKLLRGTKALTEVIPLTEEAELELAENREILKEPVHGVYYDPSKDLIAEIQKQGQGQWTYQIYQEPFKNLKTGKYARMRGAHTNDVKQLTEAVQKITTESIVIWGKTPKFKLPIQKETWETWWTEYWQATWIPEWEFVNTPPLVKLWYQ

Source Source

Source organism organism	Human immunodeficiency virus type 1
Common name common_name	HIV-1
NCBI taxonomy ID ncbi_taxonomy_id	11678
Host organism host_organism	Escherichia coli

Entity 3 Entity 3 polymer

Description description	5'-D(TPGPGPAPCPGPGPCPGPCPCPCPGPAPAPCPAPGPGPGPAPCPTPG)-3'
Molecular weight formula_weight	8392.4 kDa
Source method src_method	syn
Copy count entity_count	2

Polymer Polymer

Polymer type type	polydeoxyribonucleotide
Chain IDs strand_id	T,E

ATGGACGGCGCCCGAACAGGGACTGTG

Entity 4 Entity 4 polymer

Description description	5'-D(CPAPGPTPCPCPCPTPGPTPTPCPGPGP(MRG)PCPGPCPCPG)-3'
Molecular weight formula_weight	6490.3 kDa
Source method src_method	syn
Copy count entity_count	2

Polymer Polymer

Polymer type type	polydeoxyribonucleotide
Chain IDs strand_id	P,F

ACAGTCCCTGTTCGGGCGCCG

Entity 5 Entity 5 branched

Description description	beta-D-fructofuranose-(2-1)-alpha-D-glucopyranose
Molecular weight formula_weight	342.3 kDa
Source method src_method	man
Copy count entity_count	2

Entity 6 Entity 6 non-polymer

Description description	MAGNESIUM ION
Molecular weight formula_weight	24.3 kDa
Source method src_method	syn
Copy count entity_count	6

Entity 7 Entity 7 non-polymer

Description description	[(1R)-2-methoxy-1-{[(1S,3R)-3-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)cyclopentyl]oxy}-2-oxoethyl]phosphonic acid
Molecular weight formula_weight	362.3 kDa
Source method src_method	syn
Copy count entity_count	2

Entity 8 Entity 8 non-polymer

Description description	SULFATE ION
Molecular weight formula_weight	96.1 kDa
Source method src_method	syn
Copy count entity_count	1

Entity 9 Entity 9 water

Description description	water
Molecular weight formula_weight	18.0 kDa
Source method src_method	nat
Copy count entity_count	6

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6. Fold Classification (SCOP + CATH) 18 domains

CATH v4.4 (18 domains)

Domain ID domain_id	4r5pA01
Class class	3 — Alpha Beta
Architecture architecture	10 — Roll
Topology topology	10 — HIV Type 1 Reverse Transcriptase; Chain A, domain 1
Homologous superfamily homologous superfamily	10 — HIV Type 1 Reverse Transcriptase, subunit A, domain 1

Domain ID domain_id	4r5pA02
Class class	3 — Alpha Beta
Architecture architecture	30 — 2-Layer Sandwich
Topology topology	70 — Alpha-Beta Plaits
Homologous superfamily homologous superfamily	270 — Reverse transcriptase/Diguanylate cyclase domain

Domain ID domain_id	4r5pA03
Class class	3 — Alpha Beta
Architecture architecture	30 — 2-Layer Sandwich
Topology topology	70 — Alpha-Beta Plaits
Homologous superfamily homologous superfamily	270 — Reverse transcriptase/Diguanylate cyclase domain

Domain ID domain_id	4r5pA04
Class class	3 — Alpha Beta
Architecture architecture	30 — 2-Layer Sandwich
Topology topology	70 — Alpha-Beta Plaits
Homologous superfamily homologous superfamily	270 — Reverse transcriptase/Diguanylate cyclase domain

Domain ID domain_id	4r5pA05
Class class	3 — Alpha Beta
Architecture architecture	30 — 2-Layer Sandwich
Topology topology	420 — Nucleotidyltransferase; domain 5
Homologous superfamily homologous superfamily	10 — Ribonuclease H-like superfamily/Ribonuclease H

Domain ID domain_id	4r5pB01
Class class	3 — Alpha Beta
Architecture architecture	10 — Roll
Topology topology	10 — HIV Type 1 Reverse Transcriptase; Chain A, domain 1
Homologous superfamily homologous superfamily	10 — HIV Type 1 Reverse Transcriptase, subunit A, domain 1

Domain ID domain_id	4r5pB02
Class class	3 — Alpha Beta
Architecture architecture	30 — 2-Layer Sandwich
Topology topology	70 — Alpha-Beta Plaits
Homologous superfamily homologous superfamily	270 — Reverse transcriptase/Diguanylate cyclase domain

Domain ID domain_id	4r5pB03
Class class	3 — Alpha Beta
Architecture architecture	30 — 2-Layer Sandwich
Topology topology	70 — Alpha-Beta Plaits
Homologous superfamily homologous superfamily	270 — Reverse transcriptase/Diguanylate cyclase domain

Domain ID domain_id	4r5pB04
Class class	3 — Alpha Beta
Architecture architecture	30 — 2-Layer Sandwich
Topology topology	70 — Alpha-Beta Plaits
Homologous superfamily homologous superfamily	270 — Reverse transcriptase/Diguanylate cyclase domain

Domain ID domain_id	4r5pC01
Class class	3 — Alpha Beta
Architecture architecture	10 — Roll
Topology topology	10 — HIV Type 1 Reverse Transcriptase; Chain A, domain 1
Homologous superfamily homologous superfamily	10 — HIV Type 1 Reverse Transcriptase, subunit A, domain 1

Domain ID domain_id	4r5pC02
Class class	3 — Alpha Beta
Architecture architecture	30 — 2-Layer Sandwich
Topology topology	70 — Alpha-Beta Plaits
Homologous superfamily homologous superfamily	270 — Reverse transcriptase/Diguanylate cyclase domain

Domain ID domain_id	4r5pC03
Class class	3 — Alpha Beta
Architecture architecture	30 — 2-Layer Sandwich
Topology topology	70 — Alpha-Beta Plaits
Homologous superfamily homologous superfamily	270 — Reverse transcriptase/Diguanylate cyclase domain

Domain ID domain_id	4r5pC04
Class class	3 — Alpha Beta
Architecture architecture	30 — 2-Layer Sandwich
Topology topology	70 — Alpha-Beta Plaits
Homologous superfamily homologous superfamily	270 — Reverse transcriptase/Diguanylate cyclase domain

Domain ID domain_id	4r5pC05
Class class	3 — Alpha Beta
Architecture architecture	30 — 2-Layer Sandwich
Topology topology	420 — Nucleotidyltransferase; domain 5
Homologous superfamily homologous superfamily	10 — Ribonuclease H-like superfamily/Ribonuclease H

Domain ID domain_id	4r5pD01
Class class	3 — Alpha Beta
Architecture architecture	10 — Roll
Topology topology	10 — HIV Type 1 Reverse Transcriptase; Chain A, domain 1
Homologous superfamily homologous superfamily	10 — HIV Type 1 Reverse Transcriptase, subunit A, domain 1

Domain ID domain_id	4r5pD02
Class class	3 — Alpha Beta
Architecture architecture	30 — 2-Layer Sandwich
Topology topology	70 — Alpha-Beta Plaits
Homologous superfamily homologous superfamily	270 — Reverse transcriptase/Diguanylate cyclase domain

Domain ID domain_id	4r5pD03
Class class	3 — Alpha Beta
Architecture architecture	30 — 2-Layer Sandwich
Topology topology	70 — Alpha-Beta Plaits
Homologous superfamily homologous superfamily	270 — Reverse transcriptase/Diguanylate cyclase domain

Domain ID domain_id	4r5pD04
Class class	3 — Alpha Beta
Architecture architecture	30 — 2-Layer Sandwich
Topology topology	70 — Alpha-Beta Plaits
Homologous superfamily homologous superfamily	270 — Reverse transcriptase/Diguanylate cyclase domain

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7. Citations (6)

Alpha-carboxy nucleoside phosphonates as universal nucleoside triphosphate mimics.

Proc.Natl.Acad.Sci.USA (2015)

PMID: 25733891 · DOI: 10.1073/pnas.1420233112 PRIMARY

;Structures of HIV-1 RT-RNA/DNA ternary complexes with dATP and nevirapine reveal conformational flexibility of RNA/DNA: insights into requirements for RNase H cleavage. ;

Nucleic Acids Res. (2014)

PMID: 24880687 · DOI: 10.1093/nar/gku487

HIV-1 reverse transcriptase complex with DNA and nevirapine reveals non-nucleoside inhibition mechanism.

Nat.Struct.Mol.Biol. (2012)

PMID: 22266819 · DOI: 10.1038/nsmb.2223

Structural basis of HIV-1 resistance to AZT by excision.

Nat.Struct.Mol.Biol. (2010)

PMID: 20852643 · DOI: 10.1038/nsmb.1908

;Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. ;

J.Biol.Chem. (2009)

PMID: 19812032 · DOI: 10.1074/jbc.M109.022525

;High-resolution structures of HIV-1 reverse transcriptase/TMC278 complexes: strategic flexibility explains potency against resistance mutations. ;

Proc.Natl.Acad.Sci.USA (2008)

PMID: 18230722 · DOI: 10.1073/pnas.0711209105

Unit-cell length a length_a	89.905 Å
Unit-cell length b length_b	133.529 Å
Unit-cell length c length_c	139.218 Å
Unit-cell angle α angle_alpha	90.00 °
Unit-cell angle β angle_beta	97.81 °
Unit-cell angle γ angle_gamma	90.00 °
Molecules per unit cell Z z_pdb	4

Space group space_group	P 1 21 1
Space-group number int_tables_number	4
Crystal system crystal_system	—

Resolution resolution	2.894 Å
Low-resolution limit resolution_low	44.536 Å
R factor r_factor	0.1965
R_work r_work	0.1949
R_free r_free	0.2506

Crystal structure of HIV-1 reverse transcriptase (RT) with DNA and a nucleoside triphosphate mimic alpha-carboxy nucleoside phosphonate inhibitor

1. Protein Identity and Related Structures Protein Identity & Related Structures

HIV-1 reverse transcriptase, p66 subunit

State in the Current Structure

Other States of the Same Protein in the Database

2. Structure Basics 2. Structure Basics

3. Official assembly/model SAXS Official SAXS Profiles

4r5p__assembly_1__model_1

4r5p__assembly_1__model_1 | I(q)

4r5p__assembly_1__model_1 | P(r) · Pending

4. Crystallography and Experiment 4. Crystallography & Experiment

Unit cell Unit Cell

Symmetry Symmetry

Refinement Refinement

Diffraction experiment Diffraction

5. Entities and Polymers Entities & Polymers (9)

Entity 1 Entity 1 polymer

Polymer Polymer

Source Source

Entity 2 Entity 2 polymer

Polymer Polymer

Source Source

Entity 3 Entity 3 polymer

Polymer Polymer

Entity 4 Entity 4 polymer

Polymer Polymer

Entity 5 Entity 5 branched

Entity 6 Entity 6 non-polymer

Entity 7 Entity 7 non-polymer

Entity 8 Entity 8 non-polymer

Entity 9 Entity 9 water

6. Fold Classification (SCOP + CATH) 18 domains

CATH v4.4 (18 domains)

7. Citations (6)

Crystal structure of HIV-1 reverse transcriptase (RT) with DNA and a nucleoside triphosphate mimic alpha-carboxy nucleoside phosphonate inhibitor

1. Protein Identity and Related Structures Protein Identity & Related Structures

HIV-1 reverse transcriptase, p66 subunit

State in the Current Structure

Other States of the Same Protein in the Database

Monomer

Homodimer

Homotetramer

Other homooligomers

Heteromeric or nucleic-acid complex

2. Structure Basics 2. Structure Basics

3. Official assembly/model SAXS Official SAXS Profiles

4r5p__assembly_1__model_1

4r5p__assembly_1__model_1 | I(q)

4r5p__assembly_1__model_1 | P(r) · Pending

4. Crystallography and Experiment 4. Crystallography & Experiment

Unit cell Unit Cell

Symmetry Symmetry

Refinement Refinement

Diffraction experiment Diffraction

5. Entities and Polymers Entities & Polymers (9)

Entity 1 Entity 1 polymer

Polymer Polymer

Source Source

Entity 2 Entity 2 polymer

Polymer Polymer

Source Source

Entity 3 Entity 3 polymer

Polymer Polymer

Entity 4 Entity 4 polymer

Polymer Polymer

Entity 5 Entity 5 branched

Entity 6 Entity 6 non-polymer

Entity 7 Entity 7 non-polymer

Entity 8 Entity 8 non-polymer

Entity 9 Entity 9 water

6. Fold Classification (SCOP + CATH) 18 domains

CATH v4.4 (18 domains)

7. Citations (6)