3MED

HIV-1 K103N Reverse Transcriptase in Complex with TMC125

PDB DOI: https://doi.org/10.2210/pdb3MED/pdb

Classification: TRANSFERASE
Organism(s): HIV-1 M:B_HXB2R
Expression System: Escherichia coli
Mutation(s): Yes

Deposited: 2010-03-31 Released: 2010-05-12
Deposition Author(s): Lansdon, E.B.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.50 Å
R-Value Free: 0.277
R-Value Work: 0.224
R-Value Observed: 0.227

Starting Model: experimental
View more details

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.4 of the entry. See complete history.

Literature

Crystal Structures of HIV-1 Reverse Transcriptase with Etravirine (TMC125) and Rilpivirine (TMC278): Implications for Drug Design.

Lansdon, E.B., Brendza, K.M., Hung, M., Wang, R., Mukund, S., Jin, D., Birkus, G., Kutty, N., Liu, X.

(2010) J Med Chem 53: 4295-4299

PubMed: 20438081 Search on PubMed
DOI: https://doi.org/10.1021/jm1002233
Primary Citation of Related Structures:
3MEC, 3MED, 3MEE, 3MEG

PubMed Abstract:
Diarylpyrimidine (DAPY) non-nucleoside reverse transcriptase inhibitors (NNRTIs) have inherent flexibility, helping to maintain activity against a wide range of resistance mutations. Crystal structures were determined with wild-type and K103N HIV-1 reverse transcriptase with etravirine (TMC125) and rilpivirine (TMC278). These structures reveal a similar binding mode for TMC125 and TMC278, whether bound to wild-type or K103N RT. Comparison to previously published structures reveals differences in binding modes for TMC125 and differences in protein conformation for TMC278.

Organizational Affiliation

Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, California 94404, USA. [email protected]

Macromolecule Content

Total Structure Weight: 116.98 kDa
Atom Count: 7,967
Modelled Residue Count: 953
Deposited Residue Count: 1,000
Unique protein chains: 2

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
p66 Reverse transcriptase	A	560	HIV-1 M:B_HXB2R	Mutation(s): 1 EC: 2.7.7.49
UniProt
Find proteins for P04585 (Human immunodeficiency virus type 1 group M subtype B (isolate HXB2)) Explore P04585 Go to UniProtKB: P04585
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P04585
Sequence Annotations Expand
Reference Sequence

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
p51 Reverse transcriptase	B	440	HIV-1 M:B_HXB2R	Mutation(s): 1 EC: 2.7.7.49
UniProt
Find proteins for P04585 (Human immunodeficiency virus type 1 group M subtype B (isolate HXB2)) Explore P04585 Go to UniProtKB: P04585
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P04585
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
65B Query on 65B Download Ideal Coordinates CCD File SDF format, chain C [auth A] MOL2 format, chain C [auth A] mmCIF format, chain C [auth A]	C [auth A]	4-({6-AMINO-5-BROMO-2-[(4-CYANOPHENYL)AMINO]PYRIMIDIN-4-YL}OXY)-3,5-DIMETHYLBENZONITRILE C₂₀ H₁₅ Br N₆ O PYGWGZALEOIKDF-UHFFFAOYSA-N		Interactions Focus chain C [auth A] Interactions & Density Focus chain C [auth A]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain D [auth A] SDF format, chain E [auth A] SDF format, chain F [auth A] SDF format, chain G [auth B] SDF format, chain H [auth B] SDF format, chain I [auth B] MOL2 format, chain D [auth A] MOL2 format, chain E [auth A] MOL2 format, chain F [auth A] MOL2 format, chain G [auth B] MOL2 format, chain H [auth B] MOL2 format, chain I [auth B] mmCIF format, chain D [auth A] mmCIF format, chain E [auth A] mmCIF format, chain F [auth A] mmCIF format, chain G [auth B] mmCIF format, chain H [auth B] mmCIF format, chain I [auth B]	D [auth A] E [auth A] F [auth A] G [auth B] H [auth B] D [auth A], E [auth A], F [auth A], G [auth B], H [auth B], I [auth B]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A] Focus chain G [auth B] Focus chain H [auth B] Focus chain I [auth B] Interactions & Density Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A] Focus chain G [auth B] Focus chain H [auth B] Focus chain I [auth B]
CL Query on CL Download Ideal Coordinates CCD File SDF format, chain J [auth B] MOL2 format, chain J [auth B] mmCIF format, chain J [auth B]	J [auth B]	CHLORIDE ION Cl VEXZGXHMUGYJMC-UHFFFAOYSA-M		Interactions Focus chain J [auth B] Interactions & Density Focus chain J [auth B]