PDBsum entry 1rzc

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Lyase(oxo-acid) PDB id
Protein chain
258 a.a.
_CU ×2
Waters ×216

References listed in PDB file
Key reference
Title X-Ray analysis of metal-Substituted human carbonic anhydrase ii derivatives.
Authors K.Håkansson, A.Wehnert, A.Liljas.
Ref. Acta Crystallogr D Biol Crystallogr, 1994, 50, 93. [DOI no: 10.1107/S0907444993008790]
PubMed id 15299481
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 86%.
Metal-substituted crystals of human carbonic anhydrase II belonging to space group P2(1) with cell dimensions a = 42.7, b = 41.7, c = 73.0 A and beta = 104.6 degrees were analyzed crystallographically. The resolution limit ranged from 1.82 to 1.92 A with high completeness (86.2-90.7%). Cobalt(II)-substituted carbonic anhydrase has a tetrahedral coordination around the metal both at pH 6 and pH 7.8, similar to the native zinc enzyme. In contrast, the catalytically inactive copper(II), nickel(II) and manganese(II) derivatives showed increased coordination number around the metal ion. Whereas the copper is best described as penta-coordinated, the nickel and manganese are best described as hexa-coordinated. The results are briefly compared with spectroscopic observations and our current view on carbonic anhydrase catalysis.
Figure 1.
Fig. 1. The active-site structure of native human carbonic anhydrase II. The conformation of the peptide chain is the same in the native enzyme and all the metal-substituted derivatives described in this paper, but the solvent structure differs among the different substitutions. Waters 263 and 338 are sometimes referred to as the 'zinc water' and 'deep water', respectively. The structure was plotted using the coordinates of HD, ansson, Carlsson, Svensson & Liljas (1992).
Figure 3.
Fig. 3. The active site of cobalt(II)-substituted carbonic anhydrase at pit 6.0. Difference electron maps were calculated after refinement of native coordinates without waters 263, 338 and 339. Positive (continuous lines) and negative (broken lines) IFol - IFcI contours were drawn at +3e. The occupancy of the sulfate was refined to 0.6.
The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (1994, 50, 93-0) copyright 1994.
Secondary reference #1
Title Structure of native and apo carbonic anhydrase ii and structure of some of its anion-Ligand complexes.
Authors K.Håkansson, M.Carlsson, L.A.Svensson, A.Liljas.
Ref. J Mol Biol, 1992, 227, 1192-1204. [DOI no: 10.1016/0022-2836(92)90531-N]
PubMed id 1433293
Full text Abstract
Figure 1.
Figure 1. The molecules involved in he hydrogen bond chain between His64 an the zinc water molecule in native carbnic anhydrase at pH 7%. Distances and angles are; 64Nd' -2920HH-3180HH: (322 A. 196.7''. 2.73 A) and 2920HH-3180HH-2630HH: (2.7 A, lOS.l'', 2.79 A).
Figure 3.
Figure 3. A larger view than in Fig. 2 of the active site. Note the ydrophobic nature of the right hand sde of the cleft ith valins 121, 143 and 207, leucines 141 and 198 and tryptophan 209.
The above figures are reproduced from the cited reference with permission from Elsevier
Secondary reference #2
Title Structure of cobalt carbonic anhydrase complexed with bicarbonate.
Authors K.Håkansson, A.Wehnert.
Ref. J Mol Biol, 1992, 228, 1212-1218. [DOI no: 10.1016/0022-2836(92)90327-G]
PubMed id 1474587
Full text Abstract
Figure 1.
Figure 1. The Co(II)carbonic anhydrasebicarbnate complex. Difference electron maps were calculated after refinement of native co-ordinates without waters molecules 263 and 338 and with Co(H) instead of Zn(II). Positive (continuous lines) and negative (broken lines) IF,/ IF,1 contours were rawn at +3a. The broken thinner molecular drawings renresent the bindinn sites for formate in native CA11 (Hbkansson et a.Z., 1992) and for bicarbonate in mant T200HUCAIi (Xue t al., 1992y.
Figure 2.
Figure 2. The carbonic anhydrase mechanism of Hakansson et ai. (1992) in stereo. The `-states'' refer to Fig. 8 in that paper. (a) (State 1) Native carbonic anhydrase II: with a zinc hydroxyl (23) at the 4th (tetrahedral) co-ordination site. b) (State 2,3) A carbon dioxide molecule (500) is bound to the enzyme and is electrophilically activated. This is the crystal structure of carbonic anhydrase complexed with cyanate (Lindahl et aZ., 19923). The broken lines represent the binding of the sulfonamide group in the carbonic anhydrseDiamo complex; which may be analogous to an early tage of nucleophilic attack on the carbon dioxide. (c) (State 4) This state s hypotheticl. The zinc hydroxyl is now a part of the bicarbonate product and is bound at the zin water position wit,h the tetrahedral geometry o t,he native enzyme. The oxygen atom itself is also tetrahedrally surrounded by water molecule 318, Thr1990Y, the zinc ion and the bicarbonate arbon atom. The position of bicaronate is similar to what is found in th mutant T200H-bicarbonate complex, although the solvent structures are different in the 2 cases (Xue et al.; 1992) (d) (State 5) Water molecule 318 is leaving its normal position and makes a long co-ordination contact with te zinc ion and is now called 263. The bicarbonate group is pushed away to a longer co-ordination distance. This is the crysta structure rported in this paper. The bicarbonate molecule is now free to leave. The zinc water then takes its tetrahedral postin and a solution molecule takes the vacant 318 osition. This step is co-ordinated with the proton shuttle (Liang & Lipscomb, 1989), where 1 of the zinc water protons is shuttled through water molecules 31%292.Hi64 and released to a nearby buffer molecule in order to omplete the cycle and regenerate the zinc hydroxide.
The above figures are reproduced from the cited reference with permission from Elsevier
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