PDBsum entry 2f1b

Hydrolase

PDB id: 2f1b

Contents

Protein chain

1014 a.a. *

Ligands

NAG

GB3

MPD

Metals

_ZN

Waters ×1158

* Residue conservation analysis

PDB id:

2f1b

Name:

Hydrolase

Title:

Golgi alpha-mannosidase ii complex with (2r,3r,4s,5r)-2-({[(1r)-2- hydroxy-1-phenylethyl]amino}methyl)-5-methylpyrrolidine-3,4-diol

Structure:

Alpha-mannosidase ii. Chain: a. Fragment: catalytic domain. Synonym: mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase, man ii, golgi alpha-mannosidase ii, aman ii. Engineered: yes

Source:

Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Gene: alpha-man-ii, gmii. Expressed in: drosophila melanogaster. Expression_system_taxid: 7227.

Resolution:

1.45Å R-factor: 0.173 R-free: 0.194

Authors:

D.A.Kuntz,D.R.Rose

Key ref:

P.Englebienne et al. (2007). Evaluation of docking programs for predicting binding of Golgi alpha-mannosidase II inhibitors: a comparison with crystallography. Proteins, 69, 160-176. PubMed id: 17557336 DOI: 10.1002/prot.21479

Date:

14-Nov-05 Release date: 05-Dec-06

Protein chain

Q24451  (MAN2_DROME) -  Alpha-mannosidase 2 from Drosophila melanogaster

Seq: 1108 a.a.

Struc: 1014 a.a.*

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

Enzyme reactions

• Enzyme class: E.C.3.2.1.114 - mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase.
• Pathway: Mannosyl-glycoprotein N-acetylglucosaminyltransferases
• Reaction: N₄-{beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->3)-[alpha- D-Man-(1->6)]-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)- beta-D-GlcNAc}-L-asparaginyl-[protein] + 2 H2O = 2 alpha-D-mannopyranose + an N₄-{beta-D-GlcNAc-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->6)]- beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-beta-D-GlcNAc}-L-asparaginyl- [protein]

DOI no: 10.1002/prot.21479

Proteins 69:160-176 (2007)

PubMed id: 17557336

Evaluation of docking programs for predicting binding of Golgi alpha-mannosidase II inhibitors: a comparison with crystallography.

P.Englebienne, H.Fiaux, D.A.Kuntz, C.R.Corbeil, S.Gerber-Lemaire, D.R.Rose, N.Moitessier.

ABSTRACT

Golgi alpha-mannosidase II (GMII), a zinc-dependent glycosyl hydrolase, is a promising target for drug development in anti-tumor therapies. Using X-ray crystallography, we have determined the structure of Drosophila melanogaster GMII (dGMII) complexed with three different inhibitors exhibiting IC50's ranging from 80 to 1000 microM. These structures, along with those of seven other available dGMII/inhibitor complexes, were then used as a basis for the evaluation of seven docking programs (GOLD, Glide, FlexX, AutoDock, eHiTS, LigandFit, and FITTED). We found that small inhibitors could be accurately docked by most of the software, while docking of larger compounds (i.e., those with extended aromatic cycles or long aliphatic chains) was more problematic. Overall, Glide provided the best docking results, with the most accurately predicted binding around the active site zinc atom. Further evaluation of Glide's performance revealed its ability to extract active compounds from a benchmark library of decoys.

Selected figure(s)

Figure 1.
Figure 1. Electron density representation of the inhibitors 8, 9 and 10 bound in the active site of dGMII. Maps are simulated annealing omit maps (F[o]-F[c]) of only the inhibitors contoured at 3.5 . For orientation purposes the active site zinc ion is represented as a magenta ball. This figure was generated with PyMOL.

Figure 2.
Figure 2. (a) Interaction of 8 with residues in the active site of dGMII. Interactions closer than 3.2 Å are indicated with cyan dotted lines; interactions with the zinc ion are indicated in magenta. Water molecules appear as orange balls. Distances are presented in Table III. This figure was generated with PyMOL.

The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (2007, 69, 160-176) copyright 2007.

Figures were selected by the author.