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PDBsum entry 1cin

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Lyase(oxo-acid) PDB id
1cin
Jmol
Contents
Protein chain
256 a.a.
Ligands
MMC
MTS
Metals
_ZN
Waters ×159

References listed in PDB file
Key reference
Title Positions of his-64 and a bound water in human carbonic anhydrase ii upon binding three structurally related inhibitors.
Authors G.M.Smith, R.S.Alexander, D.W.Christianson, B.M.Mckeever, G.S.Ponticello, J.P.Springer, W.C.Randall, J.J.Baldwin, C.N.Habecker.
Ref. Protein Sci, 1994, 3, 118-125. [DOI no: 10.1002/pro.5560030115]
PubMed id 8142888
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 percentage match of 97%.
Abstract
The 3-dimensional structure of human carbonic anhydrase II (HCAII; EC 4.2.1.1) complexed with 3 structurally related inhibitors, 1a, 1b, and 1c, has been determined by X-ray crystallographic methods. The 3 inhibitors (1a = C8H12N2O4S3) vary only in the length of the substituent on the 4-amino group: 1a, proton; 1b, methyl; and 1c, ethyl. The binding constants (Ki's) for 1a, 1b, and 1c to HCAII are 1.52, 1.88, and 0.37 nM, respectively. These structures were solved to learn if any structural cause could be found for the difference in binding. In the complex with inhibitors 1a and 1b, electron density can be observed for His-64 and a bound water molecule in the native positions. When inhibitor 1c is bound, the side chain attached to the 4-amino group is positioned so that His-64 can only occupy the alternate position and the bound water is absent. While a variety of factors contribute to the observed binding constants, the major reason 1c binds tighter to HCAII than does 1a or 1b appears to be entropy: the increase in entropy when the bound water molecule is released contributes to the increase in binding and overcomes the small penalty for putting the His-64 side chain in a higher energy state.
Figure 1.
Fig. 1. Inhibitorstructures la, Ib, and IC, showing the numbering scheme used or of theinhibitors and referenced in Table 2.
Figure 4.
Fig. 4. Stereo views of the 1F, 1 - IF, I omit contoured at 20 for inhibitors la (A), Ib (B), and IC (C).
The above figures are reprinted from an Open Access publication published by the Protein Society: Protein Sci (1994, 3, 118-125) copyright 1994.
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