2R4F: 3-hydroxy-3-methylglutaryl-coenzyme A reductase

Substituted Pyrazoles as Hepatselective HMG-COA reductase inhibitors. Determined by X-ray diffraction at 1.7 Å resolution. Released 29 Apr 2008.

Method

X-ray diffraction

Resolution

1.7 Å

Organism

Homo sapiens

Chains

4

Atoms

13,374

Mol. weight

192.4 kDa

Ligands

RIE

Released

29 Apr 2008

Explore 2R4F in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

2R4F contains 83 α-helices and 84 β-strands across 4 chains. Residue ranges use author residue numbering, as in the PDB file, from PDBe. To see them in 3D, choose the Cartoon representation with Secondary structure coloring: helices, sheets and coils get different colors.

Chain A: 23 helices, 21 β-strands

Molecules and chains

>2R4F_1 3-hydroxy-3-methylglutaryl-coenzyme A reductase (chains A, B, C, D)
HHHHHHEPRPNEECLQILGNAEKGAKFLSDAEIIQLVNAKHIPAYKLETLIETHERGVSI
RRQLLSKKLSEPSSLQYLPYRDYNYSLVMGACCENVIGYMPIPVGVAGPLCLDEKEFQVP
MATTEGCLVASTNRGCRAIGLGGGASSRVLADGMTRGPVVRLPRACDSAEVKAWLETSEG
FAVIKEAFDSTSRFARLQKLHTSIAGRNLYIRFQSRSGDAMGMNMISKGTEKALSKLHEY
FPEMQILAVSGNYCTDKKPAAINWIEGRGKSVVCEAVIPAKVVREVLKTTTEAMIEVNIN
KNLVGSAMAGSIGGYNAHAANIVTAIYIACGQDAAQNVGSSNCITLMEASGPTNEDLYIS
CTMPSIEIGTVGGGTNLLPQQACLQMLGVQGACKDNPGENARQLARIVCGTVMAGELSLM
AALAAGHLVKSHMIHNRSKIN

Ligands and cofactors

Water and common crystallization additives (SO4) are not listed.

Primary citation

Substituted pyrazoles as hepatoselective HMG-CoA reductase inhibitors: discovery of (3R,5R)-7-[2-(4-fluoro-phenyl)-4-isopropyl-5-(4-methyl-benzylcarbamoyl)-2H-pyrazol-3-yl]-3,5-dihydroxyheptanoic acid (PF-3052334) as a candidate for the treatment of hypercholesterolemia. Pfefferkorn, J.A., Choi, C., Larsen, S.D. et al. J Med Chem (2008) 51:31-45. DOI 10.1021/jm070849r · PubMed

Related structures

Other PDB entries of the same protein (UniProt P04035 (AlphaFold model), which also has an AlphaFold model), best resolution first:

• 3CCZ 1.7 Å, Thermodynamic and structure guided design of statin hmg-coa reductase inhibitors
• 1DQA 2.0 Å, Complex of the catalytic portion of human hmg-CoA reductase with hmg, CoA, and NADP+
• 2Q6B 2.0 Å, Design and synthesis of novel, conformationally restricted HMG-COA reductase inhibitors
• 2Q6C 2.0 Å, Design and synthesis of novel, conformationally restricted HMG-COA reductase inhibitors
• 2Q1L 2.05 Å, Design and Synthesis of Pyrrole-based, Hepatoselective HMG-CoA Reductase Inhibitors
• 3CD7 2.05 Å, Thermodynamic and structure guided design of statin hmg-coa reductase inhibitors
• 8S6B 2.06 Å, CryoEM structure of Apo form of catalytic domain of human HMG-CoA reductase
• 3CDA 2.07 Å, Thermodynamic and structure guided design of statin hmg-coa reductase inhibitors
• 1DQ8 2.1 Å, Complex of the catalytic portion of human hmg-CoA reductase with hmg and CoA
• 1HW8 2.1 Å, Complex of the catalytic portion of human hmg-CoA reductase with compactin (also known…
• 1HWL 2.1 Å, Complex of the catalytic portion of human hmg-CoA reductase with rosuvastatin (formally…
• 3CCW 2.1 Å, Thermodynamic and structure guided design of statin hmg-coa reductase inhibitors

Browse structure collections

About this viewer

MolViewer shows 2R4F directly in your browser with nothing to install. Switch between cartoon, ball-and-stick, spacefill and surface views, color by chain, secondary structure or B-factor, measure distances, angles and dihedrals, and share or embed the view.