PDBsum entry 1sip

Hydrolase(acid proteinase)

PDB id: 1sip

Contents

Protein chain

99 a.a. *

Waters ×40

* Residue conservation analysis

PDB id:

1sip

Name:

Hydrolase(acid proteinase)

Title:

Alternative native flap conformation revealed by 2.3 angstroms resolution structure of siv proteinase

Structure:

Unliganded siv protease. Chain: a. Engineered: yes

Source:

Simian immunodeficiency virus. Organism_taxid: 11723. Cell_line: s2. Organ: leaves

Biol. unit:

Dimer (from PQS)

Resolution:

2.30Å R-factor: 0.170

Authors:

A.F.Wilderspin

Key ref:

A.F.Wilderspin and R.J.Sugrue (1994). Alternative native flap conformation revealed by 2.3 A resolution structure of SIV proteinase. J Mol Biol, 239, 97. PubMed id: 8196050

Date:

13-Apr-94 Release date: 31-Aug-94

Protein chain

Q88016  (Q88016_SIVM3) -  Pol polyprotein (Fragment) from Simian immunodeficiency virus

Seq: 1060 a.a.

Struc: 99 a.a.*

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

Enzyme reactions

• Enzyme class 2: E.C.3.1.13.2 - exoribonuclease H.
• Reaction: Exonucleolytic cleavage to 5'-phosphomonoester oligonucleotides in both 5'- to 3'- and 3'- to 5'-directions.
• Enzyme class 3: E.C.3.1.26.13 - retroviral ribonuclease H.

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

J Mol Biol 239:97 (1994)

PubMed id: 8196050

Alternative native flap conformation revealed by 2.3 A resolution structure of SIV proteinase.

A.F.Wilderspin, R.J.Sugrue.

ABSTRACT

A large conformational change is observed between HIV-1 proteinase in the ligand-free state and in complexes with transition-state inhibitors. Crystal structures of this enzyme have either the flaps open for the native or ligand-free enzyme or the flaps closed for peptidomimetic ligand-bound enzyme. We describe the structure of native recombinant SIV proteinase which like other retroviral proteinases crystallizes as a perfect 2-fold symmetric dimer but in a different crystal packing arrangement. In contrast to HIV-1 PR we show that SIV proteinase in the ligand-free state adopts the closed flaps conformation, demonstrating that ligand binding is not a prerequisite for the closed flaps conformation. The catalytic water was clearly observed between the two aspartates which were not perfectly co-planar, and in this structure the active site cleft is more restricted than for either inhibitor bound or ligand-free HIV-1 proteinase. Accommodation of two bulkier side-chains in the simian enzyme core has resulted in a more exposed N terminus than for HIV-1 PR which we predict could enhance autocatalytic cleavage at the N terminus.