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PDBsum entry 1hug

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Lyase(oxo-acid) PDB id
1hug
Jmol
Contents
Protein chain
256 a.a.
Ligands
AUC ×4
Metals
_ZN
Waters ×231

References listed in PDB file
Key reference
Title Differences in anionic inhibition of human carbonic anhydrase i revealed from the structures of iodide and gold cyanide inhibitor complexes.
Authors V.Kumar, K.K.Kannan, P.Sathyamurthi.
Ref. Acta Crystallogr D Biol Crystallogr, 1994, 50, 731-738. [DOI no: 10.1107/S0907444994001873]
PubMed id 15299369
Note In the PDB file this reference is annotated as "TO BE PUBLISHED". The citation details given above were identified by an automated search of PubMed on title and author names, giving a perfect match.
Abstract
The crystal structures of two anionic inhibitor complexes of human carbonic anhydrase I (HCAI), namely, HCAI-iodide and HCAI-Au(CN)(2)(-), have been refined by the restrained least-squares method at 2.2 and 2 A nominal resolution, respectively, with good stereochemistry for the final models. The R values have improved from 30.3 to 16.6% for HCAI-iodide and from 28.8 to 17.1% for HCAI-Au(CN)(2)(-). The sites of inhibitor binding as elucidated are totally different in the two structures. The iodide anion replaces the zinc-bound H(2)O/OH(-) ligand and renders the enzyme inactive. This result confirms that the zinc-bound H(2)O/OH(-) is the activity-linked group in carbonic anhydrase enzymes. Au(CN)(2)(-) binds at a different and new site near the zinc ion, without liganding to the metal. The N atom of Au(CN)(2)(-) is within hydrogen-bonding distance of the zinc-bound H(2)O/OH(-) group which shifts by about 0.4 A away from the zinc ion in relation to its position in the native HCAI. It is proposed that the presence of the inhibitor Au(CN)(2)(-) results in a conformational reorientation of the activity-linked group, due to hydrogen-bond formation with the inhibitor, which in turn sterically hinders the binding of the substrate CO(2) molecule in the active site, leading to the inhibition of HCAI enzyme.
Figure 3.
Fig. 3. Electron density in the (Fo- Fc) 'omit' map for the active-site Au(CN)2 anion and the activity-linked H20/OH- group in HCAI-Au(CN)z-. Contours are drawn at the +40" level.
Figure 4.
Fig. 4. The active site in HCAI enzyme. Also shown are binding sites of inhibitors I and Au(CN)2 .
The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (1994, 50, 731-738) copyright 1994.
Added reference #1*
Title Structure of a Kunitz-type chymotrypsin from winged bean seeds at 2.95 A resolution.
Authors J.K.Dattagupta, A.Podder, C.Chakrabarti, U.Sen, S.K.Dutta, M.Singh.
Ref. Acta Crystallogr D Biol Crystallogr, 1996, 52, 521-528. [DOI no: 10.1107/S0907444996000224]
PubMed id 15299674
Full text Abstract
Figure 5.
Fig. 5. The hydrophobic core of the /3-barrel seen down the barrel axis.
Figure 6.
Fig. 6. Hydrogen bonding (indicated by lines) in the reactive- site loop. water O atom is indicated by a dark
The above figures are reproduced from the cited reference with permission from the IUCr
*Note, "added" references are those not in the PDB file but which have either been obtained from the journal or suggested by the author(s).
Secondary reference #1
Title Structure of human carbonic anhydrase complexed with gold cyanide inhibitor: inhibition mechanism
Authors V.Kumar, K.K.Kannan.
Ref. acta crystallogr ,sect a, 1993, 49, 92.
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