PDBsum entry: 1b3a

Anti-HIV protein

PDB id: 1b3a

Contents

Protein chains

67 a.a. *

Ligands

SO4 ×4

AOP ×2

Waters ×223

* Residue conservation analysis

PDB id:

1b3a

Name:

Anti-HIV protein

Title:

Total chemical synthesis and high-resolution crystal structure of the potent anti-HIV protein aop-rantes

Structure:

Protein (rantes). Chain: a, b. Engineered: yes. Other_details: oxime link between aop group and pro3

Source:

Synthetic: yes

Biol. unit:

Dimer (from PQS)

Resolution:

1.60Å R-factor: 0.175 R-free: 0.241

Authors:

J.Wilken,D.Hoover,D.A.Thompson,P.N.Barlow,H.Mcsparron, L.Picard,A.Wlodawer,J.Lubkowski,S.B.H.Kent

Key ref:

J.Wilken et al. (1999). Total chemical synthesis and high-resolution crystal structure of the potent anti-HIV protein AOP-RANTES. Chem Biol, 6, 43-51. PubMed id: 9889151 DOI: 10.1016/S1074-5521(99)80019-2

Date:

07-Dec-98 Release date: 23-Apr-99

Protein chains

P13501  (CCL5_HUMAN) -  C-C motif chemokine 5

Seq: 91 a.a.

Struc: 67 a.a.

 Gene Ontology (GO) functional annotation 

• Cellular component: extracellular region (4 terms)
• Biological process: cellular response to fibroblast growth factor stimulus (96 terms)
• Biochemical function: chemoattractant activity (15 terms)

DOI no: 10.1016/S1074-5521(99)80019-2

Chem Biol 6:43-51 (1999)

PubMed id: 9889151

Total chemical synthesis and high-resolution crystal structure of the potent anti-HIV protein AOP-RANTES.

J.Wilken, D.Hoover, D.A.Thompson, P.N.Barlow, H.McSparron, L.Picard, A.Wlodawer, J.Lubkowski, S.B.Kent.

ABSTRACT

BACKGROUND: RANTES is a CC-type chemokine protein that acts as a chemoattractant for several kinds of leukocytes, playing an important pro-inflammatory role. Entry of human immunodeficiency virus-1 (HIV-1) into cells depends on the chemokine receptor CCR5. RANTES binds CCR5 and inhibits HIV-1 entry into peripheral blood cells. Interaction with chemokine receptors involves a distinct set of residues at the amino terminus of RANTES. This finding was utilized in the development of a chemically modified aminooxypentane derivative of RANTES, AOP-RANTES, that was originally produced from the recombinant protein using semisynthetic methods. RESULTS: AOP-RANTES has been produced by a novel total chemical synthesis that provides efficient, direct access to large amounts of this anti-HIV protein analog. The crystal structure of chemically synthesized AOP-RANTES has been solved and refined at 1.6 A resolution. The protein is a dimer, with the amino-terminal pentane oxime moiety clearly defined. CONCLUSIONS: Total chemical synthesis of AOP-RANTES provides a convenient method of producing the multi-milligram quantities of this protein needed to investigate the molecular basis of receptor binding and antiviral activity. This work provides the first truly high-resolution structure of a RANTES protein, although the structure of RANTES was known from previous nuclear magnetic resonance (NMR) determinations.