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首页> 外文期刊>Journal of Molecular Biology >CRYSTAL AND MOLECULAR STRUCTURES OF HUMAN PROGASTRICSIN AT 1.62 ANGSTROM RESOLUTION
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CRYSTAL AND MOLECULAR STRUCTURES OF HUMAN PROGASTRICSIN AT 1.62 ANGSTROM RESOLUTION

机译：人类前泌素在1.62角分辨率下的晶体和分子结构

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The crystal and molecular structures of human progastricsin (hPGC) have been determined using multiple isomorphous replacement methods and anomalous scattering in conjunction with a phased translation function. The structure has been refined to a conventional R-factor (=Sigma parallel to F-o - F-c parallel to/SigmaF-o) of 0.179 with data to 1.62 Angstrom resolution. The first 37 amino acid residues of the prosegment are similar in conformation to the equivalent residues of porcine pepsinogen (pPGN). As in pPGN, the N-zeta atom of Lys37p sits between the active-site carboxylate groups of Asp32 and Asp217, thereby preventing catalysis. The side-chains of Tyr38p and Tyr9 sit in the S1' and S1 substrate-binding pockets of hPGC, respectively, in an analogous manner to what is observed in porcine pepsinogen. There are large conformational differences centered around the region containing residues Arg39p to Pro6, relative to the equivalent region in the structure of pPGN. Two surface loops in the vicinity of this segment are also displaced relative to those in pPGN and in mature aspartic proteinases (Phe71 to Thr81 (the ''flap''), and Tyr125 to Thr131). In hPGC, Tyr75 O-eta does not make its usual hydrogen bond to Trp39 N-epsilon l. Rather, the ''flap'' containing Tyr75 is excluded from the active site by the polypeptide segment Arg39p to Pro6. However, the conformation of the inhibitory segment, Lys37p to Tyr38p, is virtually identical with that observed in pPGN. Hence the structures of these two proteins indicate that aspartic proteinase zymogens keep themselves inactive at neutral pH by a very similar mechanism in human progastricsin and porcine pepsinogen. This similarity likely carries over to all members of both the pepsinogen A and C families of aspartic proteinase zymogens. [References: 91]
机译：已使用多种同晶置换方法和反常散射结合相移功能确定了人类胃泌素（hPGC）的晶体和分子结构。该结构已精炼到0.179的常规R因子（=平行于F-o 的Sigma-平行于/ Sigma F-o的 -f-c），数据分辨率为1.62埃。该段的前37个氨基酸残基与猪胃蛋白酶原（pPGN）的等效残基相似。如在pPGN中一样，Lys37p的N-zeta原子位于Asp32和Asp217的活性位羧酸酯基之间，从而防止了催化作用。 Tyr38p和Tyr9的侧链分别位于hPGC的S1'和S1底物结合口袋中，类似于在猪胃蛋白酶原中观察到的方式。相对于pPGN结构中的等效区域，在包含残基Arg39p至Pro6的区域周围存在较大的构象差异。相对于pPGN和成熟的天冬氨酸蛋白酶（Phe71至Thr81（“襟翼”）和Tyr125至Thr131），该区段附近的两个表面环也被置换。在hPGC中，Tyr75 O-eta不与Trp39N-ε1形成通常的氢键。相反，含有Tyr75的“襟翼”被Pro6的多肽片段Arg39p从活性位点排除。然而，抑制区段Lys37p到Tyr38p的构象实际上与在pPGN中观察到的构象相同。因此，这两种蛋白质的结构表明天冬氨酸蛋白酶酶原通过在人类胃泌素和猪胃蛋白酶原中的非常相似的机制使其在中性pH下无活性。这种相似性可能会延续到天冬氨酸蛋白酶酶原的胃蛋白酶原A和C家族的所有成员。 [参考：91]

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